RAND appropriateness panel to determine the applicability of UK guidelines on the management of acute respiratory distress syndrome (ARDS) and other strategies in the context of the COVID-19 pandemic.

BACKGROUND: COVID-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. METHODS: An 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. RESULTS: Disagreement 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. CONCLUSION: The expert panel found no reason to deviate from the evidence-based supportive strategies for managing ARDS outlined in recent guidelines.

ECLS Training and Simulation - Evaluation of the 8th Educational Corner of the EuroELSO Congress 2019 Held in Barcelona.

Introduction: Simulation-based learning and hands-on learning are popular in medicine, particularly in areas where life-saving manoeuvres and team skills are required. Simulations can be provided in different environments: directly in hospitals (in situ), in dedicated facilities (simulation rooms) or, on occasion, at scientific meetings, thus taking advantage of the delegates' motivation. Simulation-based learning in extracorporeal life support is also increasingly relevant due to the inherent features of the often difficult and emergent decision-making, approaches and management involved, as well as to the challenging multidisciplinary teamwork. Aim: Based on these premises and on the constant rise in interest in starting new extracorporeal life support programmes, the EuroELSO organization has, since the beginning of its scientific activities, established an 'ad hoc' space (Educational Corner) for training and hands-on sessions with a limited number of attendees per session during its annual congress. Methods: Experienced trainers deliver repeated dedicated sessions on fundamental aspects of extracorporeal life support management. After several years of sessions, a questionnaire was prepared and delivered to the attendees at the 8th annual congress in Barcelona. Results: More than 90% of the responders indicated that they would recommend the workshop to their colleagues and that they received useful information during the workshops. Over 85% of the responders (85-97%) indicated that the workshops met the set educational goals and objectives and indicated that the simulation sessions would have a positive impact on their daily practice. Conclusion: The Educational Corner during the EuroELSO Congress has achieved great popularity, as shown by the number of attendees participating each year, and presumably improves many technical and behavioural skills among the attendees.

Routine CT scanning of patients retrieved to a tertiary centre on veno-venous extracorporeal membrane oxygenation: a retrospective risk benefit analysis.

INTRODUCTION: Comprehensive clinical examination can be compromised in patients on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Adjunctive diagnostic imaging strategies range from bedside imaging only to routine computed tomography (CT). The risk-benefit of either approach remains to be evaluated. Patients retrieved to the Royal Brompton Hospital (RBH) on VV-ECMO routinely undergo admission CT imaging of head, chest, abdomen and pelvis. This study aimed to identify how frequently changes in therapy or adverse events could be attributed to routine CT scanning. METHODS: Demographic and clinical data were gathered retrospectively from patients retrieved to RBH on VV-ECMO (January 2014-2016). Scans were categorized as 'routine' or requested to clarify a specific clinical uncertainty. Clinical records were reviewed to identify attributable management changes and CT- related adverse events. Seventy-two patients were retrieved on VV-ECMO (median age 44 years) and 65 scanned on admission (mean radiation dose 2344mGy-cm). Routine head CT head yielded novel clinical information in 11 patients, 10 of whom had unexpected intracranial haemorrhage and, subsequently, had their anticoagulation withheld. Routine thoracic CT identified unexpected positive findings in three patients (early fibrosis, pulmonary vasculitis, pneumomediastinum), eliciting management variation in one (steroid administration). Routine abdomen/pelvis CT identified new information in three patients (adrenal haemorrhage, hepatosteatosis, splenic infarction), changing the management in one (withholding anticoagulation). RESULTS: CT scanning was not associated with consequential adverse events (e.g. accidental decannulation, gas entrainment into the circuit, hypoxia, hypotension). Median transfer/scan time was 78 minutes, requiring five ITU staff-members. In our cohort, a policy of routine head CT changed the management in 17% of patients; the yield from routine chest, abdomen and pelvis CT was modest. CT transfer was safe, but resource intensive. CONCLUSION: Prospective studies should evaluate whether routine CT impacts outcome.

Predictors of outcome in patients with cystic fibrosis requiring endotracheal intubation.

BACKGROUND AND OBJECTIVE: Acute severe clinical deterioration of patients with cystic fibrosis (CF) may mandate endotracheal intubation. The benefits of intubation were evaluated by examining which pre-admission parameters were associated with intensive care unit (ICU) outcome and assessing the potential benefits of intubation for survivors in terms of time from ICU discharge to death. METHODS: A retrospective analysis of data from a single centre was undertaken. RESULTS: Thirty patients required intubation on 34 occasions (8 per 1000 admissions). Eleven patients died in ICU and 7 after ICU but not hospital discharge. Fifty-nine per cent of 22 patients intubated for pneumothorax and/or haemoptysis survived to hospital discharge. Of the twelve intubated for infective exacerbations, 33% survived to hospital discharge. Those who died after hospital discharge survived 447 days. There were no significant differences for survivors in reasons for intubation, colonizing organism, frequency of infective exacerbations, severity of illness or pulmonary physiology. Osteoporosis and a greater fall in body mass index over the 24 months prior were more frequent in non-survivors. CONCLUSIONS: Patients with CF developing haemoptysis and/or pneumothorax should be admitted to ICU and intubated promptly, should this be required. Chronic disease markers may be more relevant prognostically than rates of hospitalization or forced expiratory volume in 1 s decline which should not be bars to invasive ventilation.

Developing key performance indicators for adult critical care transfer services: Scoping review and Delphi technique.

In 2021 NHS England commissioned regional Adult Critical Care Transfer Services. These services will replace a historically predominant ad hoc approach to adult critical care transfers nationally. It is anticipated that these new formal services will provide a system of robust regional & national governance previously acknowledged to be deficient. As part of this process, it is important that an agreed set of transfer service quality indicators are developed to drive equitable improvement in patient care. We used a Delphi technique to develop a set of key performance indicators through consensus for a recently established London critical care transfer service. We believe this may be the first-time key performance indicators have been developed for adult critical care transfer services using a consensus method. We hope services will consider tracking similar measures to enable benchmarking and drive improvements in patient care.

Pathophysiology of pulmonary hypertension in acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI.

Free haemoglobin in 'old' transfused blood - baddy or bystander?

In the previous issue of Critical Care, Vermeulen Windsant and colleagues demonstrate that transfusion of packed red cells is associated with a transient increase in plasma free haemoglobin and scavenging of nitric oxide in vitro. They also demonstrate that older units of blood have more free haemoglobin in their supernatants. Whether the administration of older stored blood results in adverse clinical outcomes is a topical clinical question. The present study proposes a mechanism for transfusion-related harm but also has implications for patients who have other sources of free haemoglobin in their circulation.

The good and the bad of diabetes mellitus in the critically ill.

Diabetes mellitus is increasingly prevalent and associated with significant end organ damage that one may presume to impact upon critical illness. However, Siegelaar and colleagues present data that suggest, excepting those patients admitted to a cardiac intensive care unit, the presence of diabetes mellitus is not associated with increased mortality in critically ill patients. It is not possible to unpick how unmeasured parameters such as glycaemic control, the nature of whether type I or type II, or concomitant drug therapy confound the results. Nevertheless, the results are consistent with many risk-adjustment models used in the critically ill, and clinical practice that tolerates mild hyperglycaemia. Is it even possible that diabetes mellitus is protective?

Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A(H1N1).

CONTEXT: Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic. OBJECTIVE: To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO. DESIGN, SETTING, AND PATIENTS: A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching). MAIN OUTCOME MEASURE: Survival to hospital discharge analyzed according to the intention-to-treat principle. RESULTS: Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated. CONCLUSION: For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.

Extracorporeal membrane oxygenation (ECMO): Radiographic appearances, complications and imaging artefacts for radiologists.

Extracorporeal membrane oxygenation (ECMO) is a form of cardiopulmonary support primarily used in cardiothoracic and intensive care unit (ICU) settings. The purpose of this review is to familiarise radiologists with the imaging features of ECMO devices, their associated complications and appropriate imaging protocols for contrast-enhanced CT imaging of ECMO patients. This paper will provide a brief introduction to ECMO and the imaging modalities utilised in ECMO patients, followed by a description of the types of ECMO available and cannula positioning. Indications and contraindications for ECMO will be outlined followed by a description of the complications associated with ECMO, which radiologists should recognise. Finally, the imaging protocol and interpretation of contrast-enhanced CT imaging in ECMO patients will be discussed. In the current clinical climate with millions of COVID-19 cases around the world and tens of thousands of critically ill patients, many requiring cardiopulmonary support in intensive care units, the use of ECMO in adults has increased, and thus so has the volume of imaging. Radiologists need to be familiar with the types of ECMO available, the correct positioning of the catheters depending on the type of ECMO being utilised, and the associated complications and imaging artefacts.

Clinician Perceptions of the Impact of a Shock Team Approach in the Management of Cardiogenic Shock: A Qualitative Study.

INTRODUCTION: Designated cross-specialty shock teams have been proposed as a mechanism to manage the complexity of decision-making and facilitate collaborative, patient-centred care-planning in cardiogenic shock. Observational data support the notion that shock protocols and teams may improve survival, but there is an absence of data interrogating how clinicians engage with and value the shock team paradigm. This study sought to explore clinician perceptions of the value of the shock call system on decision making and the management of CGS. MATERIALS & METHODS: A descriptive qualitative approach was used. A focus group, semi-structured interview was conducted with twelve cross-specialty members of a shock team at a single tertiary cardiac centre in the UK. The focus group was audio-recorded, transcribed, and thematically analysed to capture and describe the clinicians' experience and perceptions of shock team discussions. RESULTS: Eight cardiac intensivists, two heart failure cardiologists, one cardiothoracic surgeon and one interventional cardiologist participated in the focus group. Four key themes were identified from the discussions: supportive decision making; team communication; governance and learning; and future directions. CONCLUSION: This study supports the notion that cross-specialty, real-time patient discussion may provide added value beyond protocolised decision making and account for the complexities of managing patients in a field where definitive, high-quality evidence to guide practice is currently limited.

Extracorporeal Cardiopulmonary Resuscitation in Adults. Interim Guideline Consensus Statement From the Extracorporeal Life Support Organization.

DISCLAIMER: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being deployed for selected patients in cardiac arrest who do not attain a native circulation with conventional CPR (ECPR). This ELSO guideline is intended to be a practical guide to implementing ECPR and the early management following establishment of ECMO support. Where a paucity of high-quality evidence exists, a consensus has been reached amongst the authors to provide guidance to the clinician. This guideline will be updated as further evidence in this field becomes available.

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review.

INTRODUCTION: Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care. METHODS: A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method. RESULTS: Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy. CONCLUSIONS: This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.

Postcardiotomy extracorporeal membrane oxygenation in a patient with Austrian syndrome.

A 43-year-old man with Austrian syndrome, the triad of infective endocarditis (IE), pneumonia and meningitis caused by Streptococcus pneumoniae, underwent emergency aortic and mitral valve replacement and closure of an aortic root abscess. Postoperatively, he required mechanical circulatory support with veno-arterial extracorporeal membrane oxygenation and an intra-aortic balloon pump. Several days after surgery, new mitral and aortic paraprosthetic leaks (PPLs) developed. These were managed conservatively, initially, but eventually required percutaneous closure 6 weeks after the initial operation. This has enabled the patient to recover to independent mobility, 20 weeks after the operation. This case illustrates a rare clinical syndrome and the devastating impact of IE. Moreover, it illustrates the successful application of extracorporeal membrane oxygenation in postcardiotomy cardiac failure and the successful treatment of PPL in a patient unfit for redo surgery.

Sub30: Protocol for the Sub30 feasibility study of a pre-hospital Extracorporeal membrane oxygenation (ECMO) capable advanced resuscitation team at achieving blood flow within 30 ​min in patients with refractory out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest carries a poor prognosis with survival less than 10% in many patient cohorts. Survival is inversely associated with duration of resuscitation as external chest compressions do not provide sufficient blood flow to prevent irreversible organ damage during a prolonged resuscitation. Extracorporeal membrane oxygenation (ECMO) instituted during cardiac arrest can provide normal physiological blood flows and is termed Extracorporeal Cardio-Pulmonary Resuscitation (ECPR). ECPR may improve survival when used with in-hospital cardiac arrests. This possible survival benefit has not been replicated in trials of out-of-hospital cardiac arrests, possibly because of the additional time it takes to transport the patient to hospital and initiate ECPR. Pre-hospital ECPR may shorten the time between cardiac arrest and physiological blood flows, potentially improving survival. It may also mitigate some of the neurological injury that many survivors suffer. METHODS: Sub30 is a prospective six patient feasibility study. The primary aim is to test whether it is possible to institute ECPR within 30 ​min of collapse in adult patients with refractory out of hospital cardiac arrest (OHCA). The secondary aims are to gather preliminary data on clinical outcomes, resource utilisation, and health economics associated with rapid ECPR delivery in order to plan any subsequent clinical investigation or clinical service. On study days a dedicated fast-response vehicle with ECPR capability will be tasked to out-of-hospital cardiac arrests in an area of London served by Barts Heart Centre. If patients suffer a cardiac arrest refractory to standard advanced resuscitation and meet eligibility criteria, ECPR will be started in the pre-hospital environment. DISCUSSION: Delivering pre-hospital ECPR within 30 ​min of an out-of-hospital cardiac arrest presents significant ethical, clinical, governance and logistical challenges. Prior to conducting an efficacy study of ECPR the feasibility of timely and safe application must be demonstrated first. Extensive planning, multiple high-fidelity multiagency simulations and a unique collaboration between pre-hospital and in-hospital institutions will allow us to test the feasibility of this intervention in London. The study has been reviewed, refined and endorsed by the International ECMO Network (ECMONet). TRIAL REGISTRATION: Clinicaltrials. gov NCT03700125, prospectively registered October 9, 2018.

A systematic literature review and meta-analysis of the effectiveness of extracorporeal-CPR versus conventional-CPR for adult patients in cardiac arrest.

INTRODUCTION: The probability of surviving a cardiac arrest remains low. International resuscitation guidelines state that extracorporeal cardiopulmonary resuscitation (ECPR) may have a role in selected patients suffering refractory cardiac arrest. Identifying these patients is challenging. This project systematically reviewed the evidence comparing the outcomes of ECPR over conventional-CPR (CCPR), before examining resuscitation-specific parameters to assess which patients might benefit from ECPR. METHOD: Literature searches of studies comparing ECPR to CCPR and the clinical parameters of survivors of ECPR were performed. The primary outcome examined was survival at hospital discharge or 30 days. A secondary analysis examined the resuscitation parameters that may be associated with survival in patients who receive ECPR (no-flow and low-flow intervals, bystander-CPR, initial shockable cardiac rhythm, and witnessed cardiac arrest). RESULTS: Seventeen of 948 examined studies were included. ECPR demonstrated improved survival (OR 0.40 (0.27-0.60)) and a better neurological outcome (OR 0.10 (0.04-0.27)) over CCPR during literature review and meta-analysis. Characteristics that were associated with improved survival in patients receiving ECPR included an initial shockable rhythm and a shorter low-flow time. Shorter no-flow, the presence of bystander-CPR and witnessed arrests were not characteristics that were associated with improved survival following meta-analysis, although the quality of input data was low. All data were non-randomised, and hence the potential for bias is high. CONCLUSION: ECPR is a sophisticated treatment option which may improve outcomes in a selected patient population in refractory cardiac arrest. Further comparative research is needed clarify the role of this potential resuscitative therapy.

Bench-to-bedside review: sepsis, severe sepsis and septic shock - does the nature of the infecting organism matter?

International guidelines concerning the management of patients with sepsis, septic shock and multiple organ failure make no reference to the nature of the infecting organism. Indeed, most clinical signs of sepsis are nonspecific. In contrast, in vitro data suggest that there are mechanistic differences between bacterial, viral and fungal sepsis, and imply that pathogenetic differences may exist between subclasses such as Gram-negative and Gram-positive bacteria. These differences are reflected in different cytokine profiles and mortality rates associated with Gram-positive and Gram-negative sepsis in humans. They also suggest that putative anti-mediator therapies may act differently according to the nature of an infecting organism. Data from some clinical trials conducted in severe sepsis support this hypothesis. It is likely that potential new therapies targeting, for example, Toll-like receptor pathways will require knowledge of the infecting organism. The advent of new technologies that accelerate the identification of infectious agents and their antimicrobial sensitivities may allow better tailored anti-mediator therapies and administration of antibiotics with narrow spectra and known efficacy.

Butanol-extracted lipoteichoic acid induces in vivo leukocyte adhesion.

Lipoteichoic acid (LTA), an immunostimulatory component of the cell walls of gram positive bacteria, has pro-inflammatory effects in vitro and in vivo. However, one in vivo study concluded that LTA had no noticeable effects on leukocyte recruitment. In this study we investigated the effects of highly purified LTA, prepared by butanol extraction (Bu-LTA) at room temperature, on in vivo leukocyte adhesion. Using intravital microscopy we measured adhesion of leukocytes in mesenteric post-capillary venules of rats and mice. Topical superfusion of Bu-LTA (1 microg/ml) in rats significantly (p<0.05) increased adhesion within 30 min. By contrast, hot phenol-extracted LTA did not increase adhesion. Alkaline hydrolysis of Bu-LTA removed alanine residues and prevented adhesion. Also, pre-administration of anti-rat beta2-integrin antibody abolished Bu-LTA-induced adhesion. Finally, intraperitoneal injection of Bu-LTA (100 microg/ml) into mice also significantly (p<0.01) increased leukocyte adhesion measured at 60 min. In conclusion, Bu-LTA with intact alanine residues promotes beta2-integrin-dependent leukocyte adhesion in vivo.

Acute lung injury outside the ICU: a significant problem.

The incidence of acute lung injury (ALI) is influenced by nature of the underlying clinical condition. The frequency with which ALI is likely to be encountered by those practicing outside the intensive care unit (ICU) setting is largely unknown. Data from the paper under discussion indicates that ALI is seen relatively frequently in general wards and can be managed there until death or recovery. In patients with predisposing illnesses directly involving the lung, progression to ALI can be rapid.