Adjunctive treatments for the management of septic shock - a narrative review of the current evidence.

Septic shock is a leading cause of death and morbidity worldwide. The cornerstones of management include prompt identification of sepsis, early initiation of antibiotic therapy, adequate fluid resuscitation and organ support. Over the past two decades, there have been considerable improvements in our understanding of the pathophysiology of sepsis and the host response, including regulation of inflammation, endothelial disruption and impaired immunity. This has offered opportunities for innovative adjunctive treatments such as vitamin C, corticosteroids and beta-blockers. Some of these approaches have shown promising results in early phase trials in humans, while others, such as corticosteroids, have been tested in large, international, multicentre randomised controlled trials. Contemporary guidelines make a weak recommendation for the use of corticosteroids to reduce mortality in sepsis and septic shock. Vitamin C, despite showing initial promise in observational studies, has so far not been shown to be clinically effective in randomised trials. Beta-blocker therapy may have beneficial cardiac and non-cardiac effects in septic shock, but there is currently insufficient evidence to recommend their use for this condition. The results of ongoing randomised trials are awaited. Crucial to reducing heterogeneity in the trials of new sepsis treatments will be the concept of enrichment, which refers to the purposive selection of patients with clinical and biological characteristics that are likely to be responsive to the intervention being tested.

A prospective multicentre observational study of adverse iatrogenic events and substandard care preceding intensive care unit admission (PREVENT).

We examined the current incidence, type, severity and preventability of iatrogenic events associated with intensive care unit admission in five hospitals in England. All unplanned adult admissions to intensive care units were prospectively reviewed over a continuous six-week period. In the week before admission, 76/280 patients (27%) experienced 104 iatrogenic events. The majority of iatrogenic events were categorised as medical (37%), drug (17%) or nursing events (17%). Seventy-seven per cent of the events were considered preventable and 80% caused or contributed to admission. Eleven events were thought to have contributed to a patient's death. The mean (SD) age of patients who had an event was greater (63 (21) years) than those who had not (57 (19) years, p = 0.023), and they had a longer median (IQR [range]) intensive care stay, 4 (1-8 [0-29]) days vs 3 (1-5 [0-20]) days, respectively, p = 0.043.

Recurrent massive pulmonary emboli in a critically ill patient with COVID-19.

We report the haematological management of a critically ill patient with coronavirus disease 2019 (COVID-19), with recurrent massive pulmonary emboli. A previous healthy 56-year-old man presented to the emergency department with severe hypoxaemic respiratory failure due to suspected COVID-19. He required invasive mechanical ventilation and transfer to the intensive care unit for increasing ventilatory requirements and cardiovascular instability. A computed tomography (CT) pulmonary angiogram demonstrated large bilateral pulmonary emboli with right heart strain, for which he received intravenous systemic thrombolysis followed by therapeutic weight-adjusted anticoagulation with low molecular weight heparin (dalteparin). Two weeks later, following an acute respiratory deterioration, a repeat CT pulmonary angiogram demonstrated a new saddle embolus with right heart strain requiring another regime of intravenous systemic thrombolysis. This occurred despite anti-Xa-guided therapeutic anticoagulation. The dose of therapeutic dalteparin was increased incrementally to an eventual dose of 12,500 units twice daily. A low threshold for radiological imaging should be considered in all COVID-19 patients with acute cardiorespiratory deterioration. Multidisciplinary team discussions highlighted aspects of balancing the risks of bleeding from anticoagulation vs. risk of death from pulmonary embolism. This report highlights the need for further research into the underlying mechanisms and optimal management of thrombotic complications in COVID-19.