The Effect of Positive Pressure Ventilation on Acute Kidney Injury in COVID-19 Patients with Acute Respiratory Distress Syndrome: An Observational Study.

INTRODUCTION: Acute kidney injury (AKI) is frequent in critically ill COVID-19 patients and is associated with a higher mortality risk. By increasing intrathoracic pressure, positive pressure ventilation (PPV) may reduce renal perfusion pressure by reducing venous return to the heart or by increasing renal venous congestion. This study's aim was to evaluate the association between AKI and haemodynamic and ventilatory parameters in COVID-19 patients with ARDS. METHODS: This is a single-centre retrospective observational study. Consecutive patients diagnosed with COVID-19 who met ARDS criteria and required invasive mechanical ventilation were enrolled. The relationship between respiratory and haemodynamic parameters influenced by PPV and AKI development was evaluated. AKI was defined according to KDIGO criteria. AKI recovery was evaluated a month after ICU admission and patients were classified as "recovered," if serum creatinine (sCr) value returned to baseline, or as having "acute kidney disease" (AKD), if criteria for AKI stage 1 or greater persisted. The 6-month all-cause mortality was collected. RESULTS: A total of 144 patients were included in the analysis. AKI occurred in 69 (48%) patients and 26 (18%) required renal replacement therapy. In a multivariate logistic regression analysis, sex, hypertension, cumulative dose of furosemide, fluid balance, and plateau pressure were independently associated with AKI. Mortality at 6 months was 50% in the AKI group and 32% in the non-AKI group (p = 0.03). Among 36 patients who developed AKI and were discharged alive from the hospital, 56% had a full renal recovery after a month, while 14%, 6%, and 14% were classified as having an AKD of stage 0, 2, and 3, respectively. CONCLUSIONS: In our cohort, AKI was independently associated with multiple variables, including high plateau pressure, suggesting a possible role of PPV on AKI development. Further studies are needed to clarify the role of mechanical ventilation on renal function.

Characterization of compliance phenotypes in COVID-19 acute respiratory distress syndrome.

BACKGROUND: Coronavirus disease 2019-associated acute respiratory distress syndrome (COVID-19 ARDS) seems to differ from the "classic ARDS", showing initial significant hypoxemia in the face of relatively preserved compliance and evolving later in a scenario of poorly compliant lungs. We tested the hypothesis that in patients with COVID-19 ARDS, the initial value of static compliance of respiratory system (Crs) (1) depends on the previous duration of the disease (i.e., the fewer days of illness, the higher the Crs and vice versa) and (2) identifies different lung patterns of time evolution and response to prone positioning. METHODS: This was a single-center prospective observational study. We enrolled consecutive mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria, admitted to intensive care unit (ICU). Patients were divided in four groups based on quartiles of initial Crs. Relationship between Crs and the previous duration of the disease was evaluated. Respiratory parameters collected once a day and during prone positioning were compared between groups. RESULTS: We evaluated 110 mechanically ventilated patients with a diagnosis of COVID-19 who met ARDS criteria admitted to our ICUs. Patients were divided in groups based on quartiles of initial Crs. The median initial Crs was 41 (32-47) ml/cmH2O. No association was found between the previous duration of the disease and the initial Crs. The Crs did not change significantly over time within each quartile. Positive end-expiratory pressure (PEEP) and driving pressure were respectively lower and greater in patients with lower Crs. Prone positioning significantly improved PaO2/FiO2 in the 4 groups, however it increased the Crs significantly only in patients in lower quartile of Crs. CONCLUSIONS: In our cohort, the initial Crs is not dependent on the previous duration of COVID-19 disease. Prone positioning improves oxygenation irrespective to initial Crs, but it ameliorates respiratory mechanics only in patients with lower Crs.

Coagulopathy and COVID-19.

SARS-CoV-2 infection is associated with frequent thrombotic events, at the micro and macro-vascular level, due to the perpetuation of a state of hypercoagulability. The so-called 'COVID-19 associated coagulopathy' (CAC) represents a key aspect in the genesis of organ damage from SARS-CoV-2. The main coagulative alterations described in the literature are represented by high levels of D-dimer and fibrinogen. Although CAC has some common features with disseminated intravascular coagulation and sepsis-induced coagulopathy, there are important differences between these clinical pictures and the phenotype of CAC is unique. The pathogenesis of CAC is complex and is affected by the strong interconnection between the inflammatory system and coagulation, in the phenomenon of immunothrombosis and thrombo-inflammation. Several mechanisms come into play, such as inflammatory cytokines, neutrophils, the complement system as well as an alteration of the fibrinolytic system. Finally, an altered platelet function and especially endothelial dysfunction also play a central role in the pathophysiology of CAC. Heparin has several potential effects in CAC, in fact in addition to the anticoagulant effect, it could have a direct antiviral effect and anti-inflammatory properties. The high incidence of thrombo-embolic phenomena despite the use of antithrombotic prophylaxis have led some experts to recommend the use of anticoagulant doses of heparin, but at present the optimal anticoagulant regimen remains to be determined.

Accuracy of intracranial pressure monitoring: systematic review and meta-analysis.

INTRODUCTION: Intracranial pressure (ICP) measurement is used to tailor interventions and to assist in formulating the prognosis for traumatic brain injury patients. Accurate data are therefore essential. The aim of this study was to verify the accuracy of ICP monitoring systems on the basis of a literature review. METHODS: A PubMed search was conducted from 1982 to 2014, plus additional references from the selected papers. Accuracy was defined as the degree of correspondence between the pressure read by the catheter and a reference "real" ICP measurement. Studies comparing simultaneous readings from at least two catheters were included. Drift was defined as the loss of accuracy over the monitoring period. Meta-analyses of data from the studies were used to estimate the overall mean difference between simultaneous ICP measurements and their variability. Individual studies were weighted using both a fixed and a random effects model. RESULTS: Of 163 articles screened, 83 compared two intracranial catheters: 64 reported accuracy and 37 drift (some reported both). Of these, 10 and 17, respectively, fulfilled the inclusion criteria for accuracy and zero drift analysis. The combined mean differences between probes were 1.5 mmHg (95 % confidence interval (CI) 0.7-2.3) with the random effects model and 1.6 mmHg (95 % CI 1.3-1.9) with the fixed effects model. The reported mean drift over a long observation period was 0.75 mmHg. No relation was found with the duration of monitoring or differences between various probes. CONCLUSIONS: This study confirms that the average error between ICP measures is clinically negligible. The random effects model, however, indicates that a high percentage of readings may vary over a wide range, with clinical implications both for future comparison studies and for daily care.

Clinical frailty scale as a predictor of outcome in elderly patients affected by moderate or severe traumatic brain injury.

Background: Older age is a well-known risk factor for unfavorable outcome in traumatic brain injury (TBI). However, many older people with TBI respond well to aggressive treatments, suggesting that chronological age and TBI severity alone may be inadequate prognostic markers. Frailty is an age-related homeostatic imbalance of loss of physiologic and cognitive reserve resulting in both limitation in autonomy of activities of daily living and vulnerability to adverse events. We hypothesized that frailty would be associated with 6-month adverse functional outcome in older people affected by moderate or severe TBI. Methods: This was a single-center prospective observational study. We enrolled consecutive patients aged ≥65 years after TBI with Glasgow Coma Scale ≤13 and admitted to our Neurosurgical Intensive Care Unit. Frailty was evaluated by Clinical Frailty Scale (CFS). Relationships between TBI severity, frailty and extended Glasgow Outcome Scale (GOSE) at 6-month were evaluated. Results: Sixty patients were studied, 65% were males, their age was 76 years (IQR 70-80) and their admission GCS was 8 (IQR 6-11) with a GCS motor score of 5 (IQR 4-5). Twenty eight were vulnerable-frail (defined as CFS ≥ 4). Vulnerable-frail patients showed greater 6-month mortality and unfavorable outcome compared to non-frail [87% vs. 30% OR and 95% CI: 15.7 (3.9-55.2), p < 0.0001 and 92% vs. 51% OR and 95% CI: 9.9 (2.1-46.3), p = 0.002]. In univariate analysis patients with unfavorable outcome were more frequently male and vulnerable-frail, had a higher prevalence of pre-existing neurodegenerative disease, abnormal pupil, lower GCS and had worst CT scan characteristics. At multivariate analysis, only CFS ≥ 4 and traumatic subarachnoid hemorrhage remained associated to 6-month outcome. Conclusion: Frailty was associated with 6 month-outcome, suggesting that the pre-injury functional status could represent an additional indicator to stratify patient's severity and to predict outcome.

Exploring alternative routes for oxygen administration.

BACKGROUND: Hypoxemia may compromise cell metabolism and organ function. Supplemental oxygen (O2) at high concentrations may prove ineffective, and issues relating to hyperoxia, barotrauma, mechanical ventilation, and extracorporeal oxygenation are well documented. Old reports suggest the potential safety and efficacy of alternative routes for O2 administration, such as intravenous or intestinal. We re-explored these routes in rat models of hypoxemia. METHODS: Hypoxemia was induced in spontaneously breathing, anesthetized rats by breathing a hypoxic gas mix (FiO2 0.1). Pilot studies infusing pure O2 gas caused early death, likely due to pulmonary embolism. Instead, rats (n = 6/group) were given intravenous O2 via a continuous infusion of pre-oxygenated Hartmann's solution (10 ml/kg/h) for 3 h with normal Ringer's lactate used in control animals. In separate experiments (n = 8/group), bowel intraluminal oxygenation was assessed with pure O2 administered through a cannula placed into the jejunal lumen at a dose of a 15 ml/kg bolus followed by a continuous infusion of 50 ml/kg/h; no treatment was given to controls. Echocardiography, arterial blood gas analysis, mean arterial pressure, muscle and liver tPO2, muscle microvascular perfused vessel density, and urine output were measured. RESULTS: Administration of oxygenated Hartmann's solution (PO2 of solution at end-experiment = 87.5 ± 1.7 kPa) was safe but did not increase either systemic or tissue oxygenation. Similarly, the administration of bowel O2 was safe but did not improve neither systemic nor liver oxygenation. CONCLUSIONS: In this rat model of hypoxemia, the intravenous infusion of gaseous O2 was unfeasible as it induced early mortality. Although safe, both intravenous infusion of oxygenated Hartmann's solution and bowel O2 administration were unable to improve arterial or tissue oxygenation.

Assessment of Fibrinolysis in Sepsis Patients with Urokinase Modified Thromboelastography.

INTRODUCTION: Impairment of fibrinolysis during sepsis is associated with worse outcome. Early identification of this condition could be of interest. The aim of this study was to evaluate whether a modified point-of-care viscoelastic hemostatic assay can detect sepsis-induced impairment of fibrinolysis and to correlate impaired fibrinolysis with morbidity and mortality. METHODS: This single center observational prospective pilot study was performed in an adult Intensive Care Unit (ICU) of a tertiary academic hospital. Forty consecutive patients admitted to the ICU with severe sepsis or septic shock were included. Forty healthy individuals served as controls. We modified conventional kaolin activated thromboelastography (TEG) adding urokinase to improve assessment of fibrinolysis in real time (UK-TEG). TEG, UK-TEG, plasminogen activator inhibitor (PAI)-1, thrombin-activatable fibrinolysis inhibitor (TAFI), d-dimer, DIC scores and morbidity (rated with the SOFA score) were measured upon ICU admission. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs) of mortality at ICU discharge. RESULTS: UK-TEG revealed a greater impairment of fibrinolysis in sepsis patients compared to healthy individuals confirmed by PAI-1. TAFI was not different between sepsis patients and healthy individuals. 18/40 sepsis patients had fibrinolysis impaired according to UK-TEG and showed higher SOFA score (8 (6-13) vs 5 (4-7), p = 0.03), higher mortality (39% vs 5%, p = 0.01) and greater markers of cellular damage (lactate levels, LDH and bilirubin). Mortality at ICU discharge was predicted by the degree of fibrinolysis impairment measured by UK-TEG Ly30 (%) parameter (OR 0.95, 95% CI 0.93-0.98, p = 0.003). CONCLUSIONS: Sepsis-induced impairment of fibrinolysis detected at UK-TEG was associated with increased markers of cellular damage, morbidity and mortality.