Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that directly stimulates T cells. Within 90 minutes after receiving a single intravenous dose of the drug, all six volunteers had a systemic inflammatory response characterized by a rapid induction of proinflammatory cytokines and accompanied by headache, myalgias, nausea, diarrhea, erythema, vasodilatation, and hypotension. Within 12 to 16 hours after infusion, they became critically ill, with pulmonary infiltrates and lung injury, renal failure, and disseminated intravascular coagulation. Severe and unexpected depletion of lymphocytes and monocytes occurred within 24 hours after infusion. All six patients were transferred to the care of the authors at an intensive care unit at a public hospital, where they received intensive cardiopulmonary support (including dialysis), high-dose methylprednisolone, and an anti-interleukin-2 receptor antagonist antibody. Prolonged cardiovascular shock and acute respiratory distress syndrome developed in two patients, who required intensive organ support for 8 and 16 days. Despite evidence of the multiple cytokine-release syndrome, all six patients survived. Documentation of the clinical course occurring over the 30 days after infusion offers insight into the systemic inflammatory response syndrome in the absence of contaminating pathogens, endotoxin, or underlying disease.

These guidelines describe a comprehensive strategy to optimize oxygenation, airway management, and tracheal intubation in critically ill patients, in all hospital locations. They are a direct response to the 4 National Audit Project of the Royal College of Anaesthetists and Difficult Airway Society, which highlighted deficient management of these extremely vulnerable patients leading to major complications and avoidable deaths. They are founded on robust evidence where available, supplemented by expert consensus opinion where it is not. These guidelines recognize that improved outcomes of emergency airway management require closer attention to human factors, rather than simply introduction of new devices or improved technical proficiency. They stress the role of the airway team, a shared mental model, planning, and communication throughout airway management. The primacy of oxygenation including pre- and peroxygenation is emphasized. A modified rapid sequence approach is recommended. Optimal management is presented in an algorithm that combines Plans B and C, incorporating elements of the Vortex approach. To avoid delays and task fixation, the importance of limiting procedural attempts, promptly recognizing failure, and transitioning to the next algorithm step are emphasized. The guidelines recommend early use of a videolaryngoscope, with a screen visible to all, and second generation supraglottic airways for airway rescue. Recommendations for emergency front of neck airway are for a scalpel-bougie-tube technique while acknowledging the value of other techniques performed by trained experts. As most critical care airway catastrophes occur after intubation, from dislodged or blocked tubes, essential methods to avoid these complications are also emphasized.

Implementing care bundles can lead to reductions in death rates in the clinical diagnostic areas targeted and in the overall hospital mortality rate.

The differentiation between ARDS(p) and ARDS(ex) can, with some caveats, be based on whether the CT appearances are typical or atypical of ARDS but not on any individual CT pattern in isolation.

IntroductionThis is the first comprehensive evaluation of Burnout Syndrome across the UK Intensive Care Unit workforce and in all three Burnout Syndrome domains: Emotional Exhaustion, Depersonalisation and lack of Personal Accomplishment.MethodsA questionnaire was emailed to UK Intensive Care Society members, incorporating the 22-item Maslach Burnout Inventory Human Services Survey for medical personnel. Burnout Syndrome domain scores were stratified by ‘risk’. Associations with gender, profession and age-group were explored.ResultsIn total, 996 multi-disciplinary responses were analysed. For Emotional Exhaustion, females scored higher and nurses scored higher than doctors. For Depersonalisation, males and younger respondents scored higher.ConclusionApproximately one-third of Intensive Care Unit team-members are at ‘high-risk’ for Burnout Syndrome, though there are important differences according to domain, gender, age-group and profession. This data may encourage a more nuanced understanding of Burnout Syndrome and more personalised strategies for our heterogeneous workforce.

ObjectiveTo describe the experience of paediatric intensive care units (PICUs) in England that repurposed their units, equipment and staff to care for critically ill adults during the first wave of the COVID-19 pandemic.DesignDescriptive study.SettingSeven PICUs in England.Main outcome measures(1) Modelling using historical Paediatric Intensive Care Audit Network data; (2) space, staff, equipment, clinical care, communication and governance considerations during repurposing of PICUs; (3) characteristics, interventions and outcomes of adults cared for in repurposed PICUs.ResultsSeven English PICUs, accounting for 137 beds, repurposed their space, staff and equipment to admit critically ill adults. Neighbouring PICUs increased their bed capacity to maintain overall bed numbers for children, which was informed by historical data modelling (median 280–307 PICU beds were required in England from March to June). A total of 145 adult patients (median age 50–62 years) were cared for in repurposed PICUs (1553 bed-days). The vast majority of patients had COVID-19 (109/145, 75%); the majority required invasive ventilation (91/109, 85%). Nearly, a third of patients (42/145, 29%) underwent a tracheostomy. Renal replacement therapy was provided in 20/145 (14%) patients. Twenty adults died in PICU (14%).ConclusionIn a rapid and unprecedented effort during the first wave of the COVID-19 pandemic, seven PICUs in England were repurposed to care for adult patients. The success of this effort was underpinned by extensive local preparation, close collaboration with adult intensivists and careful national planning to safeguard paediatric critical care capacity.

These data suggest a trend toward higher mortality and ventilatory requirements in ARDS of direct etiology, generating a hypothesis worthy of further exploration.

BackgroundCOVID-19 has become the most common cause of acute respiratory distress syndrome (ARDS) worldwide. Features of the pathophysiology and clinical presentation partially distinguish it from ‘classical’ ARDS. A Research and Development (RAND) analysis gauged the opinion of an expert panel about the management of ARDS with and without COVID-19 as the precipitating cause, using recent UK guidelines as a template.MethodsAn 11-person panel comprising intensive care practitioners rated the appropriateness of ARDS management options at different times during hospital admission, in the presence or absence of, or varying severity of SARS-CoV-2 infection on a scale of 1–9 (where 1–3 is inappropriate, 4–6 is uncertain and 7–9 is appropriate). A summary of the anonymised results was discussed at an online meeting moderated by an expert in RAND methodology. The modified online survey comprising 76 questions, subdivided into investigations (16), non-invasive respiratory support (18), basic intensive care unit management of ARDS (20), management of refractory hypoxaemia (8), pharmacotherapy (7) and anticoagulation (7), was completed again.ResultsDisagreement between experts was significant only when addressing the appropriateness of diagnostic bronchoscopy in patients with confirmed or suspected COVID-19. Adherence to existing published guidelines for the management of ARDS for relevant evidence-based interventions was recommended. Responses of the experts to the final survey suggested that the supportive management of ARDS should be the same, regardless of a COVID-19 diagnosis. For patients with ARDS with COVID-19, the panel recommended routine treatment with corticosteroids and a lower threshold for full anticoagulation based on a high index of suspicion for venous thromboembolic disease.ConclusionThe expert panel found no reason to deviate from the evidence-based supportive strategies for managing ARDS outlined in recent guidelines.