Routine Metagenomics Service for ICU Patients with Respiratory Infection.

Rationale: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Objectives: Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. Methods: RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London. Measurements and Main Results: During the first 15 weeks, RMg provided same-day results for 110 samples (86%), with a median turnaround time of 6.7 hours (interquartile range = 6.1-7.5 h). RMg was 93% sensitive and 81% specific for clinically relevant pathogens compared with routine testing. Forty-eight percent of RMg results informed antimicrobial prescribing changes (22% escalation; 26% deescalation) with escalation based on speciation in 20 out of 24 cases and detection of acquired-resistance genes in 4 out of 24 cases. Fastidious or unexpected organisms were reported in 21 samples, including anaerobes (n = 12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus, and Legionella pneumophila ST1326, which was subsequently isolated from the bedside water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A), and Aspergillus fumigatus with multiple treatments and public health impacts. Conclusions: This pilot study illustrates the potential of RMg testing to provide benefits for antimicrobial treatment, infection control, and public health when provided in a real-world critical care setting. Multicenter studies are now required to inform future translation into routine service.

"Bridging the Gap" international ECLS training and simulation - evaluation of the 10th educational corner on EuroELSO congress 2022 in London, United Kingdom.

Introduction: Simulation training offers an authentic team-based learning opportunity without risk to real patients. The Educational Corner at the annual congress of the European Branch of Extracorporeal Life Support Organisation (EuroELSO) provided an opportunity for multiple simulation training sessions facilitated by experts from all over the world.Aim: We aimed to review the educational impact of EuroELSO Educational Corner and whether it provides a quality ECLS training to a wide spectrum of multidisciplinary international attendees utilising high and low fidelity simulation, workshops and hands on sessions.Methods: During the congress, 43 sessions were conducted dedicated to ECLS education with identified educational objectives. The sessions focused on management of adults and children on V-V or V-A ECMO. Adult sessions covered emergencies on mechanical circulatory support with management of LVAD and Impella, managing refractory hypoxemia on V-V ECMO, emergencies on ECMO, renal replacement therapy on ECMO, V-V ECMO, ECPR cannulation and performing perfect simulation. Paediatric sessions covered ECPR neck and central cannulation, renal replacement on ECMO, troubleshooting, cannulation workshop, V-V recirculation, ECMO for single ventricle, PIMS-TS and CDH, ECMO transport and neurological injury.Results: The Educational Corner was attended by more than 400 participants over the two congress days. Majority of responders (88%) reported that training sessions met the set educational goals and objectives and that this would change their current practice. Almost all (94%) reported that they received useful information and 95% would recommend the session to their colleagues.Conclusion: The Educational Corner, as an integral component of the annual EuroELSO congress, achieved the set educational goals and provided quality education based on the recipient survey. Structured multidisciplinary ECLS education with standardised curriculum and feedback is an important key step in delivering quality training to an international audience. Standardisation of European ECLS education remains an important focus of the EuroELSO.

Bronchoscopic Endobronchial Valve Therapy for Persistent Air Leaks in COVID-19 Patients Requiring Veno-Venous Extracorporeal Membrane Oxygenation.

COVID-19 acute respiratory distress syndrome (ARDS) can be associated with extensive lung damage, pneumothorax, pneumomediastinum and, in severe cases, persistent air leaks (PALs) via bronchopleural fistulae (BPF). PALs can impede weaning from invasive ventilation or extracorporeal membrane oxygenation (ECMO). We present a series of patients requiring veno-venous ECMO for COVID-19 ARDS who underwent endobronchial valve (EBV) management of PAL. This is a single-centre retrospective observational study. Data were collated from electronic health records. Patients treated with EBV met the following criteria: ECMO for COVID-19 ARDS; the presence of BPF causing PAL; air leak refractory to conventional management preventing ECMO and ventilator weaning. Between March 2020 and March 2022, 10 out of 152 patients requiring ECMO for COVID-19 developed refractory PALs, which were successfully treated with bronchoscopic EBV placement. The mean age was 38.3 years, 60% were male, and half had no prior co-morbidities. The average duration of air leaks prior to EBV deployment was 18 days. EBV placement resulted in the immediate cessation of air leaks in all patients with no peri-procedural complications. Weaning of ECMO, successful ventilator recruitment and removal of pleural drains were subsequently possible. A total of 80% of patients survived to hospital discharge and follow-up. Two patients died from multi-organ failure unrelated to EBV use. This case series presents the feasibility of EBV placement in severe parenchymal lung disease with PAL in patients requiring ECMO for COVID-19 ARDS and its potential to expedite weaning from both ECMO and mechanical ventilation, recovery from respiratory failure and ICU/hospital discharge.

Evaluating the potential for respiratory metagenomics to improve treatment of secondary infection and detection of nosocomial transmission on expanded COVID-19 intensive care units.

BACKGROUND: Clinical metagenomics (CMg) has the potential to be translated from a research tool into routine service to improve antimicrobial treatment and infection control decisions. The SARS-CoV-2 pandemic provides added impetus to realise these benefits, given the increased risk of secondary infection and nosocomial transmission of multi-drug-resistant (MDR) pathogens linked with the expansion of critical care capacity. METHODS: CMg using nanopore sequencing was evaluated in a proof-of-concept study on 43 respiratory samples from 34 intubated patients across seven intensive care units (ICUs) over a 9-week period during the first COVID-19 pandemic wave. RESULTS: An 8-h CMg workflow was 92% sensitive (95% CI, 75-99%) and 82% specific (95% CI, 57-96%) for bacterial identification based on culture-positive and culture-negative samples, respectively. CMg sequencing reported the presence or absence of ß-lactam-resistant genes carried by Enterobacterales that would modify the initial guideline-recommended antibiotics in every case. CMg was also 100% concordant with quantitative PCR for detecting Aspergillus fumigatus from 4 positive and 39 negative samples. Molecular typing using 24-h sequencing data identified an MDR-K. pneumoniae ST307 outbreak involving 4 patients and an MDR-C. striatum outbreak involving 14 patients across three ICUs. CONCLUSION: CMg testing provides accurate pathogen detection and antibiotic resistance prediction in a same-day laboratory workflow, with assembled genomes available the next day for genomic surveillance. The provision of this technology in a service setting could fundamentally change the multi-disciplinary team approach to managing ICU infections. The potential to improve the initial targeted treatment and rapidly detect unsuspected outbreaks of MDR-pathogens justifies further expedited clinical assessment of CMg.

Extracorporeal membrane oxygenation in a patient with newly diagnosed acute myeloblastic leukaemia presenting with severe respiratory failure.

Veno-venous extracorporeal membrane oxygenation (ECMO) is typically instituted in severe respiratory failure, defined by Lung Injury Score, and caused either by pulmonary or extra-pulmonary reversible disease processes. These processes will have led to acute worsening of oxygenation and/or respiratory acidosis together with an inability to provide safe, lung protective, mechanical ventilation. Patients with underlying chronic immunosuppression or haematological malignancies treated with ECMO for severe respiratory failure have poor short- and long-term functional and survival outcomes. Consequently, in many centres, a diagnosis of haematological malignancy is considered a contraindication to provision of ECMO support for severe respiratory failure. We present a case of a 51-year-old female who attended her local hospital with symptoms suggestive of community-acquired pneumonia. Within a few days, there was progression to severe respiratory failure, initially managed with invasive mechanical ventilation but rapidly deteriorating respiratory failure triggered referral for ECMO support. Initial investigations on ECMO demonstrated features of acute myeloblastic leukaemia with a superimposed community-acquired pneumonia. This was successfully managed with supportive treatment alongside mechanical respiratory therapy and targeted chemotherapy, achieving complete remission and full functional recovery.

Veno-venous extracorporeal membrane oxygenation in coronavirus disease 2019: a case series.

BACKGROUND: The use of veno-venous extracorporeal membrane oxygenation (VV-ECMO) in severe hypoxaemic respiratory failure from coronavirus disease 2019 (COVID-19) has been described, but reported utilisation and outcomes are variable, and detailed information on patient characteristics is lacking. We aim to report clinical characteristics, management and outcomes of COVID-19 patients requiring VV-ECMO, admitted over 2 months to a high-volume centre in the UK. METHODS: Patient information, including baseline characteristics and clinical parameters, was collected retrospectively from electronic health records for COVID-19 VV-ECMO admissions between 3 March and 2 May 2020. Clinical management is described. Data are reported for survivors and nonsurvivors. RESULTS: We describe 43 consecutive patients with COVID-19 who received VV-ECMO. Median age was 46 years (interquartile range 35.5-52.5) and 76.7% were male. Median time from symptom onset to VV-ECMO was 14 days (interquartile range 11-17.5). All patients underwent computed tomography imaging, revealing extensive pulmonary consolidation in 95.3%, and pulmonary embolus in 27.9%. Overall, 79.1% received immunomodulation with methylprednisolone for persistent maladaptive hyperinflammatory state. Vasopressors were used in 86%, and 44.2% received renal replacement therapy. Median duration on VV-ECMO was 13 days (interquartile range 8-20). 14 patients died (32.6%) and 29 survived (67.4%) to hospital discharge. Nonsurvivors had significantly higher d-dimer (38.2 versus 9.5 mg·L-1, fibrinogen equivalent units; p=0.035) and creatinine (169 versus 73 µmol·L-1; p=0.022) at commencement of VV-ECMO. CONCLUSIONS: Our data support the use of VV-ECMO in selected COVID-19 patients. The cohort was characterised by high degree of alveolar consolidation, systemic inflammation and intravascular thrombosis.

COVID-19-related organ dysfunction and management strategies on the intensive care unit: a narrative review.

The coronavirus disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence, and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume severe respiratory failure centre in London.

Probable Vertical Transmission of SARS-CoV-2 Infection.

BACKGROUND: To date, although neonatal infections with severe acute respiratory syndrome coronovirus 2 (SARS-CoV-2) have been described, none of these have been proven to be the result of vertical transmission of SARS-CoV-2. METHODS: We describe the probable vertical transmission of SARS-CoV-2 in a neonate born to a mother with coronavirus disease 2019 (COVID-19). RESULTS: Following cesarean section, the neonate was kept in strict isolation. Molecular tests for SARS-CoV-2 on respiratory samples, blood, and meconium were initially negative, but positive on a nasopharyngeal aspirate on the third day of life. On day 5, the neonate developed fever and coryza, which spontaneously resolved. Viral genomic analysis from the mother and neonate showed identical sequences except for 1 nucleotide. CONCLUSION: This report has important implications for infection control and clinical management of pregnant women with COVID-19 and their newborns.

Faecal microbiota transplantation for refractory C lostridium difficile infection.

Faecal microbiota transplantation (FMT) has become a part of the treatment algorithm for Clostridium difficile infection (CDI), particularly for recurrent infections when antibiotics have diminishing efficacy. Notably, despite a significant proportion of patients suffering from refractory disease, there is a general lack of evidence describing the use of FMT in this patient cohort. We present here a case of successful treatment of refractory CDI in a patient under critical care.

Lung Recruitability in Severe Acute Respiratory Distress Syndrome Requiring Extracorporeal Membrane Oxygenation.

OBJECTIVES: Quantification of potential for lung recruitment may guide the ventilatory strategy in acute respiratory distress syndrome. However, there are no quantitative data on recruitability in patients with severe acute respiratory distress syndrome who require extracorporeal membrane oxygenation. We sought to quantify potential for lung recruitment and its relationship with outcomes in this cohort of patients. DESIGN: A single-center, retrospective, observational cohort study. SETTING: Tertiary referral severe respiratory failure center in a university hospital in the United Kingdom. PATIENTS: Forty-seven adults with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: In patients with severe acute respiratory distress syndrome-mainly of pulmonary origin (86%)-the potential for lung recruitment and the weight of nonaerated, poorly aerated, normally aerated, and hyperaerated lung tissue were assessed at low (5 cmH2O) and high (45 cmH2O) airway pressures. Patients were categorized as high or low potential for lung recruitment based on the median potential for lung recruitment value of the study population. The median potential for lung recruitment was 24.3% (interquartile range = 11.4-37%) ranging from -2% to 76.3% of the total lung weight. Patients with potential for lung recruitment above the median had significantly shorter extracorporeal membrane oxygenation duration (8 vs 13 d; p = 0.013) and shorter ICU stay (15 vs 22 d; p = 0.028), but mortality was not statistically different (24% vs 46%; p = 0.159). CONCLUSIONS: We observed significant variability in potential for lung recruitment in patients with severe acute respiratory distress syndrome requiring extracorporeal membrane oxygenation. Patients with high potential for lung recruitment had a shorter ICU stay and shorter extracorporeal membrane oxygenation duration.

Safety of Percutaneous Dilatational Tracheostomy During Veno-Venous Extracorporeal Membrane Oxygenation Support in Adults With Severe Respiratory Failure.

OBJECTIVES: To investigate the safety of percutaneous dilatational tracheostomy in severe respiratory failure patients during veno-venous 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 PO2 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 PO2 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 PO2 is an independent predictor of major complications following percutaneous dilatational tracheostomy.

Refractory septic shock: our pragmatic approach.

Despite timely intervention, there exists a small subgroup of patients with septic shock who develop progressive multi-organ failure. Seemingly refractory to conventional therapy, they exhibit a very high mortality. Such patients are often poorly represented in large clinical trials. Consequently, good evidence for effective treatment strategies is lacking. In this article, we describe a pragmatic, multi-faceted approach to managing patients with refractory septic shock based on our experience of toxin-mediated sepsis in a specialist referral centre. Many components of this strategy are inexpensive and widely accessible, and so may offer an opportunity to improve outcomes in these critically ill patients.

Severe Respiratory Failure, Extracorporeal Membrane Oxygenation, and Intracranial Hemorrhage.

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 (g/L) (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.

Caulobacter PopZ forms an intrinsically disordered hub in organizing bacterial cell poles.

Despite their relative simplicity, bacteria have complex anatomy at the subcellular level. At the cell poles of Caulobacter crescentus, a 177-amino acid (aa) protein called PopZ self-assembles into 3D polymeric superstructures. Remarkably, we find that this assemblage interacts directly with at least eight different proteins, which are involved in cell cycle regulation and chromosome segregation. The binding determinants within PopZ include 24 aa at the N terminus, a 32-aa region near the C-terminal homo-oligomeric assembly domain, and portions of an intervening linker region. Together, the N-terminal 133 aa of PopZ are sufficient for interacting with all binding partners, even in the absence of homo-oligomeric assembly. Structural analysis of this region revealed that it is intrinsically disordered, similar to p53 and other hub proteins that organize complex signaling networks in eukaryotic cells. Through live-cell photobleaching, we find rapid binding kinetics between PopZ and its partners, suggesting many pole-localized proteins become concentrated at cell poles through rapid cycles of binding and unbinding within the PopZ scaffold. We conclude that some bacteria, similar to their eukaryotic counterparts, use intrinsically disordered hub proteins for network assembly and subcellular organization.

Perioperative Extracorporeal Membrane Oxygenation to Facilitate Lung Resection After Contralateral Pneumonectomy.

A 75-year-old man previously underwent pneumonectomy for lung cancer. He subsequently had colorectal adenocarcinoma, and resection of metastases from his remaining lung was performed. Venovenous extracorporeal membrane oxygenation was used for perioperative respiratory support to facilitate intraoperative deflation of the remaining lung and optimization of the surgical field. Venovenous extracorporeal membrane oxygenation was continued postoperatively, allowing immediate extubation, thus avoiding strain on suture lines. Advantages, and potential risks, of venovenous extracorporeal membrane oxygenation for thoracic surgery are discussed.

Intracardiac Right-to-Left Shunt Impeding Liberation From Veno-Venous Extracorporeal Membrane Oxygenation: Two Case Studies.

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.