Abstract
Rev Bras Ter Intensiva. 2020;32(3):333-336
DOI 10.5935/0103-507X.20200061
Abstract
Rev Bras Ter Intensiva. 2020;32(3):337-347
DOI 10.5935/0103-507X.20200060
Pro-inflammatory markers play a significant role in the disease severity of patients with COVID-19. Thus, anti-inflammatory therapies are attractive agents for potentially combating the uncontrolled inflammatory cascade in these patients. We designed a trial testing tocilizumab versus standard of care intending to improve the outcomes by inhibiting interleukin-6, an important inflammatory mediator in COVID-19.
This open-label multicentre randomized controlled trial will compare clinical outcomes of tocilizumab plus standard of care versus standard of care alone in patients with moderate to severe COVID-19. Two of the following four criteria are required for protocol enrolment: D-dimer > 1,000ng/mL; C reactive protein > 5mg/dL, ferritin > 300mg/dL, and lactate dehydrogenase > upper limit of normal. The primary objective will be to compare the clinical status on day 15, as measured by a 7-point ordinal scale applied in COVID-19 trials worldwide. The primary endpoint will be assessed by an ordinal logistic regression assuming proportional odds ratios adjusted for stratification variables (age and sex).
The TOCIBRAS protocol was approved by local and central (national) ethical committees in Brazil following current national and international guidelines/directives. Each participating center had the study protocol approved by their institutional review boards before initiating protocol enrolment. The data derived from this trial will be published regardless of the results. If proven active, this strategy could alleviate the consequences of the inflammatory response in COVID-19 patients and improve their clinical outcomes.
Abstract
Rev Bras Ter Intensiva. 2020;32(3):348-353
DOI 10.5935/0103-507X.20200062
A novel coronavirus emerged this year as a cause of viral pneumonia. The main characteristics of the virus are rapid transmission, high contagion capacity and potential severity. The objective of this case series study is to describe the clinical characteristics of patients with confirmed coronavirus disease (COVID-19) admitted to different intensive care units in Argentina for mechanical ventilation.
A descriptive, prospective, multicenter case series study was conducted between April 1 and May 8, 2020. Data from patients older than 18 years who were admitted to the intensive care unit for mechanical ventilation for acute respiratory failure with a positive diagnosis of COVID-19 were included.
The variables for 47 patients from 31 intensive care units were recorded: 78.7% were men (median age of 61 years), with a SAPS II score of 43 and a Charlson index score of 3. The initial ventilatory mode was volume control - continuous mandatory ventilation with a tidal volume less than 8mL/kg in 100% of cases, with a median positive end-expiratory pressure of 10.5cmH2O. At the end of the study, 29 patients died, 8 were discharged, and 10 remained hospitalized. The SAPS II score was higher among patients who died (p = 0.046). Charlson comorbidity index was associated with higher mortality (OR = 2.27, 95% CI 1.13 - 4.55, p = 0.02).
Patients with COVID-19 and on mechanical ventilation in this series presented clinical variables similar to those described to date in other international reports. Our findings provide data that may predict outcomes.
Abstract
Rev Bras Ter Intensiva. 2020;32(3):354-362
DOI 10.5935/0103-507X.20200063
The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV-2 infection (coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop acute respiratory distress syndrome. Several clinical trials evaluated the role of corticosteroids in non-COVID-19 acute respiratory distress syndrome with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe acute respiratory distress syndrome due to confirmed or probable COVID-19.
This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48 hours before randomization) moderate or severe acute respiratory distress syndrome, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (Intervention Group) or standard treatment without dexamethasone (Control Group). Patients in the intervention group will receive dexamethasone 20mg intravenous once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until intensive care unit discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment Score evaluation at 48 hours, 72 hours and 7 days and intensive care unit -free days within 28.
Abstract
Rev Bras Ter Intensiva. 2020;32(3):363-373
DOI 10.5935/0103-507X.20200064
To investigate whether reactive hyperemia measured by peripheral arterial tonometry correlates with markers of endothelial dysfunction and may be used to identify sepsis in critical illness.
A prospective study was performed using a cohort of critically ill patients. Endothelial dysfunction was assessed on admission by quantifying reactive hyperemia-peripheral arterial tonometry and plasma levels of endothelin-1, soluble E-selectin, endocan and syndecan-1. Septic patients were compared to patients without evidence of infection.
Fifty-eight septic patients were compared to 28 controls. The natural logarithm of reactive hyperemia-peripheral arterial tonometry was negatively correlated with cardiovascular comorbidities, disease severity and plasma levels of soluble E-selectin (p = 0.024) and syndecan-1 (p < 0.001). The natural logarithm of reactive hyperemia-peripheral arterial tonometry was lower in septic patients than in controls (0.53 ± 0.48 versus 0.69 ± 0.42, respectively). When adjusted for age, the multivariable model predicted that each 0.1-unit decrease in natural logarithm of reactive hyperemia-peripheral arterial tonometry increased the odds for infection by 14.6%. m.
Reactive hyperemia-peripheral arterial tonometry is closely related to soluble E-selectin and syndecan-1, suggesting an association between endothelial activation, glycocalyx degradation and vascular reactivity. Reactive hyperemia-peripheral arterial tonometry appears to be compromised in critically ill patients, especially those with sepsis.
Abstract
Rev Bras Ter Intensiva. 2020;32(3):374-380
DOI 10.5935/0103-507X.20200065
To evaluate whether the decrease in blood pressure caused by the increase in the positive end-expiratory pressure corresponds to the pulse pressure variation as an indicator of fluid responsiveness.
This exploratory study prospectively included 24 patients with septic shock who were mechanically ventilated and subjected to three stages of elevation of the positive end-expiratory pressure: from 5 to 10cmH2O (positive end-expiratory pressure level 1), from 10 to 15cmH2O (positive end-expiratory pressure level 2), and from 15 to 20cmH2O (positive end-expiratory pressure level 3). Changes in systolic blood pressure, mean arterial pressure, and pulse pressure variation were evaluated during the three maneuvers. The patients were classified as responsive (pulse pressure variation ≥ 12%) or unresponsive to volume replacement (pulse pressure variation < 12%).
The best performance at identifying patients with pulse pressure variation ≥ 12% was observed at the positive end-expiratory pressure level 2: -9% systolic blood pressure variation (area under the curve 0.73; 95%CI: 0.49 - 0.79; p = 0.04), with a sensitivity of 63% and specificity of 80%. Concordance was low between the variable with the best performance (variation in systolic blood pressure) and pulse pressure variation ≥ 12% (kappa = 0.42; 95%CI: 0.19 - 0.56). The systolic blood pressure was < 90mmHg at positive end-expiratory pressure level 2 in 29.2% of cases and at positive end-expiratory pressure level 3 in 41.63% of cases.
Variations in blood pressure in response to the increase in positive end-expiratory pressure do not reliably reflect the behavior of the pulse pressure as a measure to identify the fluid responsiveness status.
Abstract
Rev Bras Ter Intensiva. 2020;32(3):381-390
DOI 10.5935/0103-507X.20200066
To evaluate the frequency of severe burnout syndrome among critical care providers and to correlate it with work engagement.
A self-administered survey including the Maslach Burnout Inventory, Depression Anxiety and Stress Scales, and Gallup questionnaire was distributed. All analyses were stratified by setting (intensive care unit or step-down unit) and by professional group (nurses versus physicians versus physiotherapists).
Between February 2017 and June 2017, 206 out of 325 invited professionals (63.4%) answered the questionnaires. Of these, 55 were physicians (26.7%), 88 were physiotherapists (42.7%) and 63 were nurses (30.6%). The frequency of severe burnout was 34.3% (27.9 - 41.4%), and no difference was found between professional groups or settings. The frequency of severe or very severe cases of depression, anxiety or stress was 12.9%, 11.4% and 10.5%, respectively. The median (interquartile range) score observed on the Gallup questionnaire was 41 (34 - 48), and no differences were found between professional groups or settings. There was a negative correlation between burnout and work engagement (r = -0.148; p = 0.035).
There is a high frequency of severe burnout among critical care providers working in the intensive care unit and step-down unit. There was a negative correlation between burnout and work engagement.
Abstract
Rev Bras Ter Intensiva. 2020;32(3):391-397
DOI 10.5935/0103-507X.20200067
To investigate the vancomycin effectiveness against gram-positive pathogens with the minimum inhibitory concentration of 1mg/L in pediatric patients based on the area under the curve and the minimum inhibitory concentration ratio > 400.
A population of 22 pediatric patients (13 boys) admitted to the pediatric intensive care unit with preserved renal function was stratified in two groups (G1 < 7 years and G2 ≥ 7 years). After the fourth dose administered of vancomycin (10 - 15mg/kg every 6 hours) was administered, two blood samples were collected (third and fifth hours), followed by serum measurement by immunoassays to investigate the pharmacokinetics and antimicrobial coverage.
There was no difference between the groups regarding dose, trough level or area under the curve. Coverage against gram-positive pathogens with a minimum inhibitory concentration of 1mg/L occurred in only 46% of patients in both groups. The pharmacokinetics in both groups were altered relative to the reference values, and the groups differed in regard to increased total body clearance and shortening of the biological half-life, which were more pronounced in younger patients.
A minimum empirical dose of 60mg/kg per day should be prescribed for pediatric patients in intensive care units with preserved renal function. The use of the ratio between the area under the curve and minimum inhibitory concentration in the evaluation of vancomycin coverage is recommended to achieve the desired outcome, since the pharmacokinetics are altered in these patients, which may impact the effectiveness of the antimicrobial.