Background:IgG4-related disease (IgG4-RD) is an immune-mediated disorder causing fibro-inflammatory lesions. Although the cause remains unknown, it may be driven by interactions between B lymphocytes and CD4+ cytotoxic and regulatory T cells and is characterized by an increase in short-lived plasmablasts, circulating antibodies, and macrophages. Standard therapy mainly includes glucocorticoids (GC), limited by toxicity with long-term use (> 6 mo), and to a lesser extent, immunosuppressives (eg, rituximab). Bruton tyrosine kinase (BTK) plays an important role in the activation of multiple immune effector cells such as B cells, mast cells, eosinophils, basophils, monocytes/macrophages, and neutrophils. Dysregulation of the activation of these immune cells results in autoimmune inflammation, tissue damage, and development of fibrosis. Rilzabrutinib is a highly selective oral BTK inhibitor that targets multiple pathways of innate and adaptive immunity (with direct effects on B-cell and FcR pathways) and has the potential to inhibit antigen presentation to autoreactive T cells.Objectives:To provide the biological rationale for rilzabrutinib in IgG4-RD.Methods:Rilzabrutinib has been evaluated in biochemical, in vitro studies, and in vivo models of inflammatory diseases. Additional support is provided by the phase 2 trial for oral rilzabrutinib in patients with pemphigus vulgaris and the phase 2 trial for oral rilzabrutinib in patients with immune thrombocytopenia (ITP).Results:Rilzabrutinib inhibited the activity of BTK and B-cell receptor in B cells (IC50 5-123 nM) and Fc gamma receptor in IgG/Fc gamma receptor-stimulated monocytes (IC50 56 nM) and blocked IgG- and IgM-mediated antibody production in enriched B cells when stimulated in T-cell dependent (anti-CD40+IL-21) and T-cell independent (TLR-9/CpG and TNP-LPS) pathways. The impact of rilzabrutinib on innate cell pathways was further confirmed by significant dose-dependent inhibition of macrophage and neutrophil-driven passive rat Arthus reaction (P < 0.01 vs vehicle) and antibody-induced murine ITP (P < 0.05 vs vehicle). In a 12-week phase 2 pemphigus vulgaris trial, 54% of patients achieved the primary endpoint, control of disease activity (CDA) on low-dose corticosteroids by week 4, and 73% achieved it by week 12. In the phase 2 trial of ITP patients (median 6 prior therapies), rilzabrutinib 400 mg bid showed rapid and sustained improvement in platelet counts and only grade 1/2-related adverse events1. In responders, platelet counts increased as early as day 8, potentially due to innate immune mechanisms. Collectively, results in both B and innate immune cells provide an initial basis for evaluating rilzabrutinib in IgG4-RD. The ongoing phase 2a study (NCT04520451) is investigating rilzabrutinib 400 mg bid (+tapered GC) vs GC control (3:1) for 12 weeks in IgG4-RD patients refractory to rituximab. The primary objective is to evaluate the safety and ability of rilzabrutinib to induce GC-free remission at week 12. Coupled with known preclinical/clinical findings, mechanistic analyses in this ongoing IgG4-RD study will profile B and other immune cell effects pre-/post-rilzabrutinib dosing to enhance the clinical understanding of rilzabrutinib in IgG4-RD.Conclusion:Studies of rilzabrutinib that show beneficial effects on both B-cell and innate cell pathways provide support for its therapeutic role in immune-mediated diseases and for targeting the underlying pathophysiological effects of IgG4-RD. Effective and safe therapies that rapidly induce and maintain clinical responses, while minimizing the need for continuous GC treatment, remain an unmet need for patients with IgG4-RD.References:[1]Kuter et al. Res Pract Thromb Haemost. 2020;4(suppl 1): PB1318.Disclosure of Interests:Li Long Employee of: Principia Biopharma, a Sanofi Company, Matthew Baker: None declared, Mollie Carruthers: None declared, Alireza Meysami: None declared, Robert Spiera Consultant of: research funding and personal fees for consulting from Chemocentryx, Formation Biologics, Roche-Genentech, and Sanofi, Grant/research support from: research funding fees from BMS, Boehringer Ingelheim, Corbus, GSK, and Inflarx; personal fees from AbbVie, CSL Behring, GSK, and Janssen, Mamatha Reddy Employee of: Principia Biopharma, a Sanofi Company, Marianne Kavanagh Employee of: Principia Biopharma, a Sanofi Company, Michelle Francesco Employee of: Principia Biopharma, a Sanofi Company, Claire Langrish Employee of: Principia Biopharma, a Sanofi Company, Ann Neale Employee of: Principia Biopharma, a Sanofi Company, Puneet Arora Employee of: Principia Biopharma, a Sanofi Company, John H. Stone Consultant of: research funding and personal fees for consulting from Principia and Sanofi

Bruton tyrosine kinase (BTK) is a critical immune signaling enzyme expressed in B and innate immune cells and is an essential element downstream of BCR and FcR signaling. Rilzabrutinib (PRN1008) is an oral, reversible, covalent BTK inhibitor that drives durable BTK occupancy with low off-target effects shown by other BTK inhibitors. Preclinical PRN1008 activity was evaluated in biochemical studies and in vivo models of inflammation and canine pemphigus. PRN1008 showed kinase selectivity for BTK with an enzyme inhibition IC50 of 1.3 nM; functional BTK target occupancy of 91% (±2%) was achieved in PBMCs at 4 h. In a skin IgG antibody (FcγR)-mediated acute Arthus reaction rat model, PRN1008 10, 20, and 40 mg/kg led to significant, dose-dependent improvements in immune complex-mediated inflammation and injury (P<0.01 all doses vs vehicle). In a passive cutaneous anaphylaxis mouse model that utilizes mechanisms similar to human allergic disease, PRN1008 20 and 40 mg/kg significantly inhibited IgE antibody (FcεR)-mediated immune responses (P<0.01 both doses vs vehicle). In naturally occurring canine pemphigus foliaceus, an autoantibody-mediated autoimmune disease that dogs and human share, 4 dogs treated with PRN1008 showed a rapid clinical improvement. All animals achieved complete or substantial disease control measurable by improved canine PDAI scores and without requiring corticosteroid use. Anti-inflammatory effects in dogs were visible within 2 wk and tolerability was excellent. BTK target occupancy in PBMCs from dogs was >70% within 4 h of PRN1008 treatment. Overall, PRN1008 preclinical results show simultaneous mechanisms of rapid and sustained anti-inflammatory effects by blocking inflammatory immune cells, eliminating autoantibody destructive signaling, and preventing new autoantibody production. These results provide a strong biologic basis for rilzabrutinib (PRN1008) in B cell- and autoantibody-driven autoimmune disorders, supporting ongoing clinical studies of pemphigus (phase 3) and immune thrombocytopenia (phase 2).

Objectives: To investigate the safety of percutaneous dilatational tracheostomy in severe respiratory failure patients during venovenous extracorporeal membrane oxygenation support. Design: A single-center, retrospective, observational cohort study. Setting: Tertiary referral severe respiratory failure center, university teaching hospital. Patients: Severe respiratory failure patients consecutively admitted and supported with veno-venous extracorporeal membrane oxygenation between January 2010 and December 2015. Intervention: A bronchoscopy-guided percutaneous dilatational tracheostomy was performed in all cases. Measurements and Main Results: Sixty-five veno-venous extracorporeal membrane oxygenation patients (median [interquartile range] age, 47 yr [interquartile range, 35-59 yr]; 39 males; Acute Physiology and Chronic Health Evaluation-II score, 18 [interquartile range, 17-22] Sequential Organ Failure Assessment score, 10 [interquartile range, 7-16]) underwent percutaneous dilatational tracheostomy. Ten patients (15%) developed one or more major complications. Of these, seven (11%) had major bleeding, and three of these also required circuit change due to extracorporeal membrane oxygenation circuit dysfunction. Two more patients (3.1%) presented with isolated extracorporeal membrane oxygenation circuit dysfunction requiring circuit change, and one developed bilateral pneumothoraces (1.5%) requiring intercostal drain insertion. Patients who developed complications had significantly lower extracorporeal membrane oxygenation postoxygenator Po-2 prior to percutaneous dilatational tracheostomy (45.8 kPa [interquartile range, 36.9-56.5 kPa] vs 57.9 kPa [interquartile range, 45.1-64.2 kPa]; p = 0.019]. On multivariate analysis, including demographic, clinical, biochemical, hematologic variables, and extracorporeal membrane oxygenation circuit functional variables, extracorporeal membrane oxygenation postoxygenator Po 2 was the only independent variable associated with major complications following percutaneous dilatational tracheostomy (beta = -0.09; odds ratio, 0.9; 95% CI, 0.84-0.99; p = 0.03). Conclusions: Percutaneous dilatational tracheostomy is associated with a considerable complication rate in veno-venous extracorporeal membrane oxygenation patients. Preprocedure circuit performance as indicated by extracorporeal membrane oxygenation postoxygenator Po 2 is an independent predictor of major complications following percutaneous dilatational tracheostomy.

Objectives: For patients supported with veno-venous extracorporeal membrane oxygenation, the occurrence of intracranial hemorrhage is associated with a high mortality. It is unclear whether intracranial hemorrhage is a consequence of the extracorporeal intervention or of the underlying severe respiratory pathology. In a cohort of patients transferred to a regional severe respiratory failure center that routinely employs admission brain imaging, we sought 1) the prevalence of intracranial hemorrhage; 2) survival and neurologic outcomes; and 3) factors associated with intracranial hemorrhage.Design: A single-center, retrospective, observational cohort study.Setting: Tertiary referral severe respiratory failure center, university teaching hospital.Patients: Patients admitted between December 2011 and February 2016.Intervention: None.Measurements and Main Results: Three hundred forty-two patients were identified: 250 managed with extracorporeal support and 92 managed using conventional ventilation. The prevalence of intracranial hemorrhage was 16.4% in extracorporeal membrane oxygenation patients and 7.6% in conventionally managed patients (p = 0.04). Multivariate analysis revealed factors independently associated with intracranial hemorrhage to be duration of ventilation (d) (odds ratio, 1.13 [95% CI, 1.03-1.23]; p = 0.011) and admission fibrinogen (gL) (odds ratio, 0.73 [0.57-0.91]; p = 0.009); extracorporeal membrane oxygenation was not an independent risk factor (odds ratio, 3.29 [0.96-15.99]; p = 0.088). In patients who received veno-venous extracorporeal membrane oxygenation, there was no significant difference in 6-month survival between patients with and without intracranial hemorrhage (68.3% vs 76.0%; p = 0.350). Good neurologic function was observed in 92%.Conclusions: We report a higher prevalence of intracranial hemorrhage than has previously been described with high level of neurologically intact survival. Duration of mechanical ventilation and admission fibrinogen, but not exposure to extracorporeal support, are independently associated with intracranial hemorrhage.

Objectives: Veno-venous extracorporeal membrane oxygenation is an increasingly used form of advanced respiratory support, but its effects on the physiology of the right heart are incompletely understood. We seek to illustrate the impact of veno-venous extracorporeal membrane oxygenation return blood flow upon the right atrium by considering the physiologic effects during interatrial shunting.Patients: Two veno-venous extracorporeal membrane oxygenation patients in whom an extracorporeal membrane oxygenation induced right-to-left interatrial shunt appears to have created a barrier to liberation from extracorporeal support.Conclusions: Veno-venous extracorporeal membrane oxygenation return flow generates a high-pressure jet that has potential to exert focal pressure upon the intra-atrial septum. In patients with potential for interatrial flow, this may lead to a right-to-left shunt, which becomes physiologically apparent only when sweep gas flow is ceased.

Objectives: Venovenous extracorporeal membrane oxygenation for patients with severe respiratory failure is increasingly common. There has been a significant change in the population, technology, and approach used for venovenous extracorporeal membrane oxygenation over the last 10 years. The objective of this study is to describe the prevalence of postdecannulation deep vein thrombosis in the cannulated vessel in adults who have received venovenous extracorporeal membrane oxygenation for severe respiratory failure.Design: A single-center, retrospective, observational cohort, electronic note review study.Setting: Tertiary referral university teaching hospital.Patients: Patients commenced on venovenous extracorporeal membrane oxygenation for severe respiratory failure.Interventions: None.Measurements and Main Results: We identified 103 patients commenced on extracorporeal membrane oxygenation with 81 survivors from December 2011 to February 2014. We performed postdecannulation venous Doppler ultrasound in 88.9% of extracorporeal membrane oxygenation survivors. The prevalence of deep vein thrombosis in the cannulated vessel following extracorporeal membrane oxygenation is 8.1/1,000 cannula days in patients who were screened.Conclusions: The prevalence of deep vein thrombosis following decannulation from extracorporeal membrane oxygenation for severe respiratory failure is clinically significant, and routine venous Doppler ultrasound following decannulation is warranted in this population.

BACKGROUNDNo consensus exists on the optimal settings of mechanical ventilation during veno-venous extracorporeal membrane oxygenation (ECMO). Our aim was to describe how mechanical ventilation and related interventions are managed by adult ECMO centres.METHODSA cross-sectional, multi-centre, international survey of 173 adult respiratory ECMO centres. The survey was generated through an iterative process and assessed for clarity, content and face validity.RESULTSOne hundred thirty-three centres responded (76.8%). Pressure control was the most commonly used mechanical ventilation mode (64.4%). Although the median PEEP was 10 cmH2O, 22.6% set PEEP <10 cmH2O and 15.5% used 15-20 cmH2O. In 63% of centres PEEP was fixed and not titrated. Recruitment maneuvres, were never used in 34.1% of centres, or used daily in 13.2%. Centres reported using either a "lung rest" (45.7%), or an "open lung" strategy (44.2%). Only 24.8% used chest CT to guide mechanical ventilation. Adjunctive treatments were never or occasionally used. Only 10% of centres extubated patients on ECMO, mainly in more experienced centres. 71.3% of centres performed tracheostomy on ECMO, with large variability in timing (most frequent on days 6-10). Only 27.1% of ECMO centres had a protocol for mechanical ventilation on ECMO.CONCLUSIONWe found large variability in ventilatory practices during ECMO. The clinicians' training background and the centres' experience had no influence on the approach to ventilation. This survey shows that well conducted studies are necessary to determine the best practice of mechanical ventilation during ECMO and its impact on patient outcome.

SummaryWe conducted a single‐centre observational study of retrievals for severe respiratory failure over 12 months. Our intensivist‐delivered retrieval service has mobile extracorporeal membrane oxygenation capabilities. Sixty patients were analysed: 34 (57%) were female and the mean (SD) age was 44.1 (13.6) years. The mean (SD) PaO2/FIO2 ratio at referral was 10.2 (4.1) kPa and median (IQR [range]) Murray score was 3.25 (3.0–3.5 [1.5–4.0]). Forty‐eight patients (80%) required veno‐venous extracorporeal membrane oxygenation at the referring centre. There were no cannulation or extracorporeal membrane oxygenation‐related complications. The median (IQR [range]) retrieval distance was 47.2 (14.9–77.0 [2.3–342.0]) miles. There were no major adverse events during retrieval. Thirty‐seven patients (77%) who received extracorporeal membrane oxygenation survived to discharge from the intensive care unit and 36 patients (75%) were alive after six months. Senior intensivist‐initiated and delivered mobile extracorporeal membrane oxygenation is safe and associated with a high incidence of survival.

Pulmonary haemorrhage (PH) is common in patients receiving mechanical ventilation and especially during ECMO, due to severe lung pathology and systemic anticoagulation. Whilst PH manifests as worsening ventilation and gas exchange, in ECMO patients who already have low tidal volume and who do not rely on pulmonary gas exchange, deterioration may not be evident until extensive airway thrombus (AT) has developed. Management of AT is challenging, with lavage, suctioning, mechanical disruption and extraction of limited efficacy in severe cases. Limited reports suggest that topical thrombolytics may have a role in the management of AT [1]. We report the safety and efficacy of endobronchial streptokinase (EBSK) in patients with extensive AT.

Extracorporeal carbon dioxide removal (ECCO2R) is an efficient technique used in the management of hypercapnic respiratory failure. Its application in mechanically ventilated patients has been studied for over 30 years. We describe a case of severe, acute exacerbation of chronic obstructive pulmonary disease (AECOPD) unresponsive to non-invasive ventilation (NIV), where initiation of ECCO2R was used effectively to prevent endotracheal intubation.

Mortality from cardiogenic shock remains high [1] and, despite a physiological rationale, intra-aortic balloon counterpulsation (IABP) has recently been shown to be ineffective in reducing mortality [2],[3]. Veno-arterial extracorporeal membrane oxygenation (V-A ECMO) may offer a survival advantage over IABP. The objective of this study was to describe the characteristics and outcomes of patients supported with IABP or Impella and to identify the characteristics of patients who die, despite mechanical assistance, for whom a proposed V-A ECMO programme may be beneficial.

Introduction Patients with interstitial lung disease (ILD) and severe respiratory failure (SRF) requiring mechanical ventilation are widely perceived to have poor outcomes. A therapeutic strategy incorporating extracorporeal membrane oxygenation (ECMO) improves all cause SRF survival. There exist no data on the use of ECMO in severe ILD. ECMO may offer lung rest, reduce the inflammatory burden associated with mechanical ventilation and allow time for effective immunosuppression. We hypothesised that the use of ECMO and early immunosuppression increases survival in patients with ILD in whom mechanical ventilation was failing. Methods Retrospective interrogation of a single centre ECMO database for patients with ILD between 2011 and 2014. Variables collected included diagnosis; immunosuppression regimen; duration of symptoms prior to ECMO initiation; serum biochemistry; clinical severity score (SOFA) and survival to ECMO decannulation, ICU discharge and at 6 months. ECMO centre admission computed tomography (CT) thorax scans were independently analysed for pattern and degree of abnormality by two radiologists. Variables were compared between responders (those who survived without lung transplant) and non responders (composite group of those who died and one patient who survived with lung transplantation). Two-tailed t-tests were used for all comparisons. Results 12 patients with an ILD diagnosis who received ECMO were identified. ECMO and ICU survival was 58.3%. The group of responders had a shorter duration of symptoms prior to ECMO (p = 0.04), a higher CRP (p = 0.046), a higher SOFA score (p = 0.01) and a lower preponderance of diffuse alveolar damage (DAD) on CT (p = 0.19) although there was no difference in overall extent of CT abnormality. (Table 1). Conclusions The use of ECMO and early immunosuppression led to a 58.3% survival in a group of ILD associated SRF who would otherwise have been highly likely to die. The responders were characterised by a more acute and more inflammatory presentation. We suggest that ECMO and immunosuppression should be considered in patients with ILD and SRF who are failing mechanical ventilation.

On 22 September 2012, a novel coronavirus, very closely related to that from a fatal case in Saudi Arabia three months previously, was detected in a previously well adult transferred to intensive care in London from Qatar with severe respiratory illness. Strict respiratory isolation was instituted. Ten days after last exposure, none of 64 close contacts had developed severe disease, with 13 of 64 reporting mild respiratory symptoms. The novel coronavirus was not detected in 10 of 10 symptomatic contacts tested.

Coronaviruses have the potential to cause severe transmissible human disease, as demonstrated by the severe acute respiratory syndrome (SARS) outbreak of 2003. We describe here the clinical and virological features of a novel coronavirus infection causing severe respiratory illness in a patient transferred to London, United Kingdom, from the Gulf region of the Middle East.

Editor—There has been a recent focus on the role of veno-venous extracorporeal membrane oxygenation (ECMO) in the management of adult patients with severe respiratory failure. Transfer to an ECMO-capable centre improves survival without severe neurological disability compared with standard management.1Peek GJ Mugford M Tiruvoipati R et al.CESAR Trial CollaborationEfficacy and economic assessment of Conventional Ventilatory Support Versus Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR): a multicentre randomised controlled trial.Lancet. 2009; 374: 1352-1363Abstract Full Text Full Text PDF Scopus (2386) Google Scholar 2Noah M Peek GJ Finney SJ et al.Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe 2009 influenza A (H1N1).J Am Med Assoc. 2011; 306: 1659-1668Crossref PubMed Scopus (633) Google Scholar However, ECMO is invasive and not without hazards including the cannula and circuit-related complications. A 42-yr-old man was transferred to our institution with community-acquired pneumonia and acute respiratory distress syndrome, causing severe respiratory failure refractory to conventional treatment. He failed to improve with high-frequency oscillation and the prone position; thus, ECMO was initiated. Femoral-jugular cannulation was performed under ultrasound guidance and image intensifier control. The drainage cannula was positioned in the inferior vena cava (IVC) with the tip at the T11/12 level. Over the following 6 h, the patient developed acutely deranged liver function tests with a marked elevation in bilirubin (53 μmol litre−1) and alanine transaminase (311 IU litre−1) concentrations. Biliary ultrasound was unremarkable and a transthoracic echocardiogram (TTE) demonstrated no signs of acute cor pulmonale. However, TTE revealed the tip of the drainage cannula to be close to the insertion of the hepatic veins, causing narrowing of the orifice with high-velocity blood flow (1.5 m s−1) (Fig. 1a and b). As a result, the cannula was withdrawn 2–3 cm under real-time TTE guidance. Echo images demonstrated an increase in lumen size by visual estimate and a reduction in blood flow velocities and turbulence on two-dimensional, spectral, and colour flow imaging (Fig. 1c and d). Within 12 h, a significant improvement in liver function tests was noted; bilirubin concentration normalized within 24 h; similarly, alanine transaminase halved in the initial 24 h and then returned to baseline within a few days. The obstruction of venous drainage of the liver (the Budd–Chiari syndrome) occurring acutely leads to jaundice, hepatomegaly, ascites, elevated liver enzymes, and encephalopathy. The Budd–Chiari syndrome may be idiopathic, due to thrombosis of the hepatic veins in thrombogenic states or extrinsic compression, for example, due to neoplasia. We are not aware that the Budd–Chiari syndrome due to ECMO cannula obstruction has been described previously. In this case, prompt clinical recognition and echocardiographic confirmation enabled immediate withdrawal of the cannula before significant or irreversible hepatic impairment occurred. Venous drainage of the liver is by the hepatic veins which enter the IVC at the T8 level, inferior to the caval opening of the diaphragm. As the cannula tip had apparently been placed at the T11/12 level, possible explanations include a parallax error during positioning, cannula movement during supine to semi-recumbent positioning, or anatomical variation. Optimal cannula positioning is crucial during ECMO, although this is not addressed in expert guidelines.3http://www.elso.med.umich.edu/Guidelines.html (accessed 4 December 2011).Google Scholar Traditionally, chest radiography has been used to assess cannula positioning; however, the difficulty in detecting cannula malposition on chest radiography has been highlighted.4Thomas TH Price R Ramaciotti C et al.Echocardiography, not chest radiography, for evaluation of cannula placement during pediatric extracorporeal membrane oxygenation.Pediatr Crit Care Med. 2009; 10: 56-59Crossref PubMed Scopus (44) Google Scholar, 5Irish MS O'Toole SJ Kapur P et al.Cervical ECMO cannula placement in infants and children: recommendations for assessment of adequate positioning and function.J Pediatr Surg. 1998; 33: 929-931Abstract Full Text PDF PubMed Scopus (23) Google Scholar, 6Barnacle AM Smith LC Hiorns MP The role of imaging during extracorporeal membrane oxygenation in paediatric respiratory failure.Am J Roentgenol. 2006; 186: 58-66Crossref PubMed Scopus (28) Google Scholar Moreover, literature suggests that there is benefit in using echocardiography to assess cannula placement.6Barnacle AM Smith LC Hiorns MP The role of imaging during extracorporeal membrane oxygenation in paediatric respiratory failure.Am J Roentgenol. 2006; 186: 58-66Crossref PubMed Scopus (28) Google Scholar 7Riccabonna M Dacar D Zobel G et al.Sonographically guided cannula positioning for extracorporeal membrane oxygenation.Pediatr Radiol. 1995; 25: 643-645Crossref PubMed Scopus (13) Google Scholar In a recent study, 12% of the patients evaluated using TTE for the cannula position were found to have malpositioning, despite being reported 'normal' on chest radiography.4Thomas TH Price R Ramaciotti C et al.Echocardiography, not chest radiography, for evaluation of cannula placement during pediatric extracorporeal membrane oxygenation.Pediatr Crit Care Med. 2009; 10: 56-59Crossref PubMed Scopus (44) Google Scholar TTE provides real-time guidance of cannula placement and surveillance of cannula migration while minimizing radiation exposure. Transoesophageal echocardiography has been described to guide positioning of the Avalon Elite (Avalon Laboratories, CA, USA) ECMO cannula.8Dolch ME Frey L Buerkle MA Weig T Wassilowsky D Irlbeck M Transoesophageal echocardiography-guided technique for extracorporeal membrane oxygenation dual-lumen catheter placement.ASAIO J. 2011; 57: 341-343Crossref PubMed Scopus (30) Google Scholar Awareness of the potential for hepatic vein obstruction and the timely recognition of abnormal cannula positioning are critical when utilizing ECMO. Given the difficulty in confirming correct cannula placement clinically, or with plain radiography, additional real-time TTE may be considered a useful adjunct to cannula placement. None declared.

By combining the educational needs of nurses, doctors and the ICU physiotherapists, we moulded a curriculum that we then integrated with the anaesthetic nontechnical skill (ANTS) system [1]. Each simulation day has a 50:50 nurse:doctor ratio along with one or two ICU physiotherapists. The day consists of a patient safety lecture, introduction to the Sim-Man (Laerdal, Orpington, Kent, UK) manikin, six 15-min scenarios and a 30–45 min debrief of each scenario. Those not directly involved watch the scenarios via a video link and all candidates are involved in each debrief, at which we address clinical questions and focus on how nontechnical skills can be improved. All candidates fill in a feedback sheet at the end of each day and this feedback is used to develop the programme to enhance future learning. Our debriefing sessions comprise a 30% technical and 70% non-technical discussion base and we achieve this using an appropriate number and type of learning goals for each scenario.