Thrombotic and haemorrhagic complications in critically ill patients with COVID-19: a multicentre observational study.

BACKGROUND: Optimal prophylactic and therapeutic management of thromboembolic disease in patients with COVID-19 remains a major challenge for clinicians. The aim of this study was to define the incidence of thrombotic and haemorrhagic complications in critically ill patients with COVID-19. In addition, we sought to characterise coagulation profiles using thromboelastography and explore possible biological differences between patients with and without thrombotic complications. METHODS: We conducted a multicentre retrospective observational study evaluating all the COVID-19 patients received in four intensive care units (ICUs) of four tertiary hospitals in the UK between March 15, 2020, and May 05, 2020. Clinical characteristics, laboratory data, thromboelastography profiles and clinical outcome data were evaluated between patients with and without thrombotic complications. RESULTS: A total of 187 patients were included. Their median (interquartile (IQR)) age was 57 (49-64) years and 124 (66.3%) patients were male. Eighty-one (43.3%) patients experienced one or more clinically relevant thrombotic complications, which were mainly pulmonary emboli (n = 42 (22.5%)). Arterial embolic complications were reported in 25 (13.3%) patients. ICU length of stay was longer in patients with thrombotic complications when compared with those without. Fifteen (8.0%) patients experienced haemorrhagic complications, of which nine (4.8%) were classified as major bleeding. Thromboelastography demonstrated a hypercoagulable profile in patients tested but lacked discriminatory value between those with and without thrombotic complications. Patients who experienced thrombotic complications had higher D-dimer, ferritin, troponin and white cell count levels at ICU admission compared with those that did not. CONCLUSION: Critically ill patients with COVID-19 experience high rates of venous and arterial thrombotic complications. The rates of bleeding may be higher than previously reported and re-iterate the need for randomised trials to better understand the risk-benefit ratio of different anticoagulation strategies.

Management of post-intubation tracheal membrane ruptures: A practical approach.

Tracheal rupture is an infrequent, severe complication of endotracheal intubation, which can be difficult to diagnose. Post-intubation tracheal rupture (PiTR) is distinct from non-iatrogenic causes of tracheobronchial trauma and often requires different treatment. The increasing adoption of pre-hospital emergency services increases the likelihood of such complications from emergency intubations. Effective management strategies for PiTR outside specialist cardiothoracic units are possible. Two cases of severe PiTR, successfully managed non-operatively on a general medical-surgical intensive care unit, illustrate a modified approach to current standards. The evidence base for PiTR is reviewed and a pragmatic management algorithm presented.

Lung Ultrasound to Monitor Disease Severity and Aid Prognostication in COVID-19 Pneumonia: A Retrospective Analysis of Serial Lung Ultrasound Assessments.

Background: The aim of this retrospective analysis was to assess if serial lung ultrasound assessments in patients with COVID-19 pneumonia, including a novel simplified scoring system, correlate with PaO2:FiO2 ratio, as a marker of disease severity, and patient outcomes. Methods: Patients treated for COVID-19 pneumonia in a tertiary intensive care unit who had a lung ultrasound assessment were included. Standardised assessments of anterior and lateral lung regions were prospectively recorded. A validated lung ultrasound score-of-aeration and a simplified scoring system based on the number of disease-free lung regions were correlated with: PaO2:FiO2 ratio, successful weaning from mechanical ventilation, and status (alive or dead) at discharge. MedCalc© statistical software was used for statistical analysis. Results: 28 patients (109 assessments) were included. Correlation was seen between score-of-aeration and PaO2:FiO2 ratio (r = -0.61, p<0.0001) and between the simplified scoring system and PaO2:FiO2 ratio (r = 0.52 p<0.0001). Achieving a score-of-aeration of ≤9/24 or ≥2 disease-free regions was associated with successful weaning from mechanical ventilation and survival to ICU discharge (accuracy of 94% and 97% respectively). Conclusion: Retrospective analysis from this small cohort of patients demonstrates that scores-of-aeration and a simplified scoring system based on the number of disease-free antero-lateral regions from serial LUS assessments correlate with PaO2:FiO2 ratio as a marker of disease severity in patients with COVID-19 pneumonia. In addition, lung ultrasound may help identify patients who will have favourable outcomes.

Leptospirosis as an important differential of pulmonary haemorrhage on the intensive care unit: a case managed with VV-ECMO.

BACKGROUND: Leptospirosis is a potentially fatal zoonosis. It can cause a wide range of symptoms, including diffuse alveolar haemorrhage which occurs in a minority of cases but carries a mortality of over 70%. These patients may present with severe acute respiratory failure. The differential diagnosis for diffuse alveolar haemorrhage is broad whereas prompt diagnosis and treatment can be lifesaving. CASE PRESENTATION: A 20-year-old previously fit and well trout farm worker presented with a 3-day history of malaise, fevers, diarrhoea, vomiting and jaundice. He developed haemoptysis, severe headaches, neck stiffness and photophobia on the day of emergency admission. He was anaemic and thrombocytopenic. Anuric acute kidney injury (urea 32, creat 507) required immediate haemofiltration. In view of progressive respiratory failure with four-quadrant lung infiltrates on imaging, he was given broad spectrum antibiotics and pulsed methylprednisolone empirically, in case of a vasculitic pulmonary-renal presentation. He was intubated within 48 h of admission. Despite attempted protective ventilatory management, he remained hypoxaemic and developed pneumomediastinum. He was retrieved to a specialist cardiorespiratory intensive care unit on femoro-femoral mobile VV-ECMO. Three days from admission, results showed positive Leptospira IgM and real-time PCR. Serial bronchoscopies showed old and fresh clots, but not the classical progressive late red tinge of the returned lavage fluid. After eight days, VV-ECMO was weaned, he was extubated three days later, and made a full recovery. At 9 months follow-up, he was clinically better, with resolution of the CT scan findings and near normal lung function, albeit with low normal gas transfer. CONCLUSIONS: Leptospirosis is a rare but important differential to be considered in diffuse alveolar haemorrhage presenting to the ICU, especially in young males. A thorough history for occupational or recreational risk factors may offer the diagnostic clue. Most patients recover fully with antibiotics. However, resulting acute severe respiratory failure can ensue. In this situation, early consideration for respiratory ECMO support offers time for clearance of endobronchial clot, parenchymal recovery, and prevention of ventilator-induced lung injury. Steroids have no clear evidence but may be used to avoid delay in treating suspected vasculitic or autoimmune causes of diffuse alveolar haemorrhage.

Immune cell expression of GABAA receptors and the effects of diazepam on influenza infection.

Benzodiazepines increase vulnerability to infection through α1 subunit dependent Υ-amino-butyric-type-A (GABAA) signalling. Immune cell expression of GABAA receptors and the effect of diazepam on influenza infection was investigated. In patients with pneumonia, α1 GABAA subunits were expressed on alveolar macrophages and blood monocytes. In mice, influenza induced dynamic changes in immune cell GABAA subunit expression: α1 subunits decreased on alveolar macrophage, but increased on monocytes, CD4+ and CD8+ T cells. Following influenza viral infection, diazepam delayed weight loss on day 3 but later increased weight loss. Viral load was unaffected but increased bacterial superinfection was noted on day 10.