Thirty percent of Covid-19 patients admitted to intensive care units present with thrombotic complications despite thromboprophylaxis. Bed rest, obesity, hypoxia, coagulopathy, and acute excessive ...inflammation are potential mechanisms reported by previous studies. Better understanding of the underlying mechanisms leading to thrombosis is crucial for developing more appropriate prophylaxis and treatment strategies.
We aimed to assess fibrinolytic activity and thrombin generation in 78 Covid-19 patients.
Forty-eight patients admitted to the intensive care unit and 30 patients admitted to the internal medicine department were included in the study. All patients received thromboprophylaxis. We measured fibrinolytic parameters (tissue plasminogen activator, PAI-1, thrombin activatable fibrinolysis inhibitor, alpha2 anti-plasmin, and tissue plasminogen activator-modified ROTEM device), thrombin generation, and other coagulation tests (D-dimer, fibrinogen, factor VIII, antithrombin).
We observed two key findings: a high thrombin generation capacity that remained within normal values despite heparin therapy and a hypofibrinolysis mainly associated with increased PAI-1 levels. A modified ROTEM is able to detect both hypercoagulability and hypofibrinolysis simultaneously in Covid-19 patients with thrombosis.
Unfortunately, current treatment remains only supportive and symptomatic 2. ...there is an urgent need for effective drugs targeting this life-threatening complication, in particular, for patients ...developing acute respiratory distress syndrome. ...it is tempting to use CsA to dampen the dysregulated immune response in the setting of COVID-19-related ARF. ...equally important, CsA binds to Cyp-D, which inhibits opening of the mitochondrial permeability transition pore (mPTP), a pathophysiological event triggered by injury (e.g., oxidative stress, hypoxia, and ischemia/reperfusion) that may compromise cell function or survival (Fig. 1) 3.
COVID-19 pneumonia typically begins with subpleural ground glass opacities with progressive extension on computerized tomography studies. Lung ultrasound is well suited to this interstitial, ...subpleural involvement, and it is now broadly used in intensive care units (ICUs). The extension and severity of lung infiltrates can be described numerically with a reproducible and validated lung ultrasound score (LUSS). We hypothesized that LUSS might be useful as a tool to non-invasively monitor the evolution of COVID-19 pneumonia at the bedside. LUSS monitoring was rapidly implemented in the management of our COVID-19 patients with RT-PCR-documented COVID-19. The LUSS was evaluated repeatedly at the bedside. We present a graphic description of the course of LUSS during COVID-19 in 10 consecutive patients admitted in our intensive care unit with moderate to severe ARDS between March 15 and 30th. LUSS appeared to be closely related to the disease progression. In successfully extubated patients, LUSS decreased and was lower than at the time of intubation. LUSS increased inexorably in a patient who died from refractory hypoxemia. LUSS helped with the diagnosis of ventilator-associated pneumonia (VAP), showing an increased score and the presence of new lung consolidations in all 5 patients with VAPs. There was also a good agreement between CT-scans and LUSS as for the presence of lung consolidations. In conclusion, our early experience suggests that LUSS monitoring accurately reflect disease progression and indicates potential usefulness for the management of COVID-19 patients with ARDS. It might help with early VAP diagnosis, mechanical ventilation weaning management, and potentially reduce the need for X-ray and CT exams. LUSS evaluation is easy to use and readily available in ICUs throughout the world, and might be a safe, cheap and simple tool to optimize critically ill COVID-19 patients care during the pandemic.
Purpose
Identifying modifiable factors for sepsis-associated encephalopathy may help improve patient care and outcomes.
Methods
We conducted a retrospective analysis of a prospective multicenter ...database. Sepsis-associated encephalopathy (SAE) was defined by a score on the Glasgow coma scale (GCS) <15 or when features of delirium were noted. Potentially modifiable risk factors for SAE at ICU admission and its impact on mortality were investigated using multivariate logistic regression analysis and Cox proportional hazard modeling, respectively.
Results
We included 2513 patients with sepsis at ICU admission, of whom 1341 (53%) had sepsis-associated encephalopathy. After adjusting for baseline characteristics, site of infection, and type of admission, the following factors remained independently associated with sepsis-associated encephalopathy: acute renal failure adjusted odds ratio (aOR) = 1.41, 95% confidence interval (CI) 1.19–1.67, hypoglycemia <3 mmol/l (aOR = 2.66, 95% CI 1.27–5.59), hyperglycemia >10 mmol/l (aOR = 1.37, 95% CI 1.09–1.72), hypercapnia >45 mmHg (aOR = 1.91, 95% CI 1.53–2.38), hypernatremia >145 mmol/l (aOR = 2.30, 95% CI 1.48–3.57), and
S. aureus
(aOR = 1.54, 95% CI 1.05–2.25). Sepsis-associated encephalopathy was associated with higher mortality, higher use of ICU resources, and longer hospital stay. After adjusting for age, comorbidities, year of admission, and non-neurological SOFA score, even mild alteration of mental status (i.e., a score on the GCS of 13–14) remained independently associated with mortality (adjusted hazard ratio = 1.38, 95% CI 1.09–1.76).
Conclusions
Acute renal failure and common metabolic disturbances represent potentially modifiable factors contributing to sepsis-associated encephalopathy. However, a true causal relationship has yet to be demonstrated. Our study confirms the prognostic significance of mild alteration of mental status in patients with sepsis.
Acute respiratory distress syndrome (ARDS) is mostly characterized by the loss of aerated lung volume associated with an increase in lung tissue and intense and complex lung inflammation. ARDS has ...long been associated with the histological pattern of diffuse alveolar damage (DAD). However, DAD is not the unique pathological figure in ARDS and it can also be observed in settings other than ARDS. In the coronavirus disease 2019 (COVID-19) related ARDS, the impairment of lung microvasculature has been pointed out. The airways, and of notice the small peripheral airways, may contribute to the loss of aeration observed in ARDS. High-resolution lung imaging techniques found that in specific experimental conditions small airway closure was a reality. Furthermore, low-volume ventilator-induced lung injury, also called as atelectrauma, should involve the airways. Atelectrauma is one of the basic tenet subtending the use of positive end-expiratory pressure (PEEP) set at the ventilator in ARDS. Recent data revisited the role of airways in humans with ARDS and provided findings consistent with the expiratory flow limitation and airway closure in a substantial number of patients with ARDS. We discussed the pattern of airway opening pressure disclosed in the inspiratory volume-pressure curves in COVID-19 and in non-COVID-19 related ARDS. In addition, we discussed the functional interplay between airway opening pressure and expiratory flow limitation displayed in the flow-volume curves. We discussed the individualization of the PEEP setting based on these findings.
Purpose
Recruitment of lung volume is often cited as the reason for using positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS) patients. We performed a systematic ...review on PEEP-induced recruited lung volume measured from inspiratory volume-pressure (VP) curves in ARDS patients to assess the prevalence of patients with PEEP-induced recruited lung volume and the mortality in recruiters and non-recruiters.
Methods
We conducted a systematic search of PubMed to identify studies including ARDS patients in which the intervention of an increase in PEEP was accompanied by measurement of the recruited volume (
V
rec
increase versus no increase) using the VP curve in order to assess the relation between
V
rec
and mortality at ICU discharge.
We first analysed the pooled data from the papers identified and then analysed individual patient level data received from the authors via personal contact. The risk of bias of the included papers was assessed using the quality in prognosis studies tool and the certainty of the evidence regarding the relationship of mortality to
V
rec
by the GRADE approach. Recruiters were defined as patients with a
V
rec
> 150 ml. A random effects model was used for the pooled data. Multivariable logistic regression analysis was used for individual patient data.
Results
We identified 16 papers with a total of 308 patients for the pooled data meta-analysis and 14 papers with a total of 384 patients for the individual data analysis. The quality of the articles was moderate. In the pooled data, the prevalence of recruiters was 74% and the mortality was not significantly different between recruiters and non-recruiters (relative risk 1.20 95% confidence intervals 0.88–1.63). The certainty of the evidence regarding this association was very low and publication bias evident. In the individual data, the prevalence of recruiters was 70%. In the multivariable logistic regression,
V
rec
was not associated with mortality but Simplified Acute Physiology Score II and driving pressure at PEEP of 5 cmH
2
O were.
Conclusion
After a PEEP increment, most patients are recruiters.
V
rec
was not associated with ICU mortality. The presence of similar findings in the individual patient level analysis and the driving pressure at PEEP of 5 cmH
2
O was associated with mortality as previously reported validate our findings. Publication bias and the lack of prospective studies suggest more research is required.
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