Adult Respiratory Failure Research Articles

Genotype‒phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. Most affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype‒phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J domain may predict a more severe phenotype.

Genotype-phenotype correlation in recessive DNAJB4 myopathy.

Protein aggregate myopathies can result from pathogenic variants in genes encoding protein chaperones. DNAJB4 is a cochaperone belonging to the heat shock protein-40 (HSP40) family and plays a vital role in cellular proteostasis. Recessive loss-of-function variants in DNAJB4 cause myopathy with early respiratory failure and spinal rigidity, presenting from infancy to adulthood. This study investigated the broader clinical and genetic spectrum of DNAJB4 myopathy. In this study, we performed whole-exome sequencing on seven patients with early respiratory failure of unknown genetic etiology. We identified five distinct pathogenic variants in DNAJB4 in five unrelated families of diverse ethnic backgrounds: three loss-of-function variants (c.547C > T, p.R183*; c.775C > T, p.R259*; an exon 2 deletion) and two missense variants (c.105G > C, p.K35N; c.181A > G, p.R61G). All patients were homozygous. All affected individuals exhibited early respiratory failure, and patients from three families had rigid spine syndrome with axial weakness in proportion to appendicular weakness. Additional symptoms included dysphagia, ankle contractures, scoliosis, neck stiffness, and cardiac dysfunction. Notably, J-domain missense variants were associated with a more severe phenotype, including an earlier age of onset and a higher mortality rate, suggesting a strong genotype-phenotype correlation. Consistent with a loss of function, the nonsense variants presented decreased stability. In contrast, the missense variants exhibited normal or increased stability but behaved as loss-of-function variants in yeast complementation and TDP-43 disaggregation assays. Our findings suggest that DNAJB4 is an emerging cause of myopathy with rigid spine syndrome of variable age of onset and severity. This diagnosis should be considered in individuals presenting with suggestive symptoms, particularly if they exhibit neck stiffness during infancy or experience respiratory failure in adults without significant limb muscle weakness. Missense variants in the J-domain may predict a more severe phenotype.

Highlights from the Respiratory Failure and Mechanical Ventilation Conference 2024.

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the third Respiratory Failure and Mechanical Ventilation Conference in February 2024. The conference covered key points of acute and chronic respiratory failure in adults. During the 3-day conference ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. In this article, lectures delivered during the event have been summarised by early career members of the Assembly and take-home messages highlighted.

139: The Utilization of Nitric Oxide for Transport of the Adult Respiratory Failure Patient for VV ECMO Support

139: The Utilization of Nitric Oxide for Transport of the Adult Respiratory Failure Patient for VV ECMO Support

Clinical characteristics and outcomes of respiratory syncytial virus-associated ARF in immunocompetent patients: A seven-year experience at a tertiary hospital in France

Respiratory syncytial virus (RSV) is widely recognized as a cause of acute respiratory failure in infants and immunocompromised patients. However, RSV can also contribute to acute respiratory failure in adults, particularly among the elderly population. The objective of this study was to analyze the clinical characteristics and outcomes of immunocompetent adults hospitalized for RSV infection. This retrospective study included all immunocompetent adult patients consecutively admitted to a tertiary care hospital with RSV-related acute respiratory failure over a seven-year period (2016-2023). Diagnosis of RSV infection was made through nasal swabs or pulmonary samples, with multiplex reverse transcription polymerase chain reaction (RT-PCR). Patients were eligible for inclusion if they required supplemental oxygen therapy for at least 48h. One hundred and four patients met the inclusion criteria. Median age [IQR] was 77 years [67-85]. Ninety-seven patients had at least one comorbidity (97/104, 93%). At the time of RSV diagnosis, 67 patients (67/104, 64%) experienced acute decompensation of a pre-existing chronic comorbidity. Antibiotics were started in 80% (77/104) of patients; however, only 16 patients had a confirmed diagnosis of bacterial superinfection. Twenty-six patients needed ventilatory support (26/104, 25%) and 21 were admitted to the intensive care unit (21/104, 20%). The median duration of oxygen therapy [IQR] was 6 days [3-9], while the median hospital length of stay [IQR] was 11 days [6-15]. The overall mortality rate within 1 month of hospital admission was 13% (14/104). The sole variables associated with one-month mortality were age and maximum oxygen flow during hospitalization. RSV-associated acute respiratory failure affected elderly individuals with multiple comorbidities and was associated with prolonged hospitalization and a high mortality rate.

The Synthetic Surfactant CHF5633 Restores Lung Function and Lung Architecture in Severe Acute Respiratory Distress Syndrome in Adult Rabbits

PurposeAcute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults. In ARDS extensive inflammation and leakage of fluid into the alveoli lead to dysregulation of pulmonary surfactant metabolism and function. Altered surfactant synthesis, secretion, and breakdown contribute to the clinical features of decreased lung compliance and alveolar collapse. Lung function in ARDS could potentially be restored with surfactant replacement therapy, and synthetic surfactants with modified peptide analogues may better withstand inactivation in ARDS alveoli than natural surfactants.MethodsThis study aimed to investigate the activity in vitro and the bolus effect (200 mg phospholipids/kg) of synthetic surfactant CHF5633 with analogues of SP‐B and SP‐C, or natural surfactant Poractant alfa (Curosurf®, both preparations Chiesi Farmaceutici S.p.A.) in a severe ARDS model (the ratio of partial pressure arterial oxygen and fraction of inspired oxygen, P/F ratio ≤ 13.3 kPa) induced by hydrochloric acid instillation followed by injurious ventilation in adult New Zealand rabbits. The animals were ventilated for 4 h after surfactant treatment and the respiratory parameters, histological appearance of lung parenchyma and levels of inflammation, oxidative stress, surfactant dysfunction, and endothelial damage were evaluated.ResultsBoth surfactant preparations yielded comparable improvements in lung function parameters, reductions in lung injury score, pro-inflammatory cytokines levels, and lung edema formation compared to untreated controls.ConclusionsThis study indicates that surfactant replacement therapy with CHF5633 improves lung function and lung architecture, and attenuates inflammation in severe ARDS in adult rabbits similarly to Poractant alfa. Clinical trials have so far not yielded conclusive results, but exogenous surfactant may be a valid supportive treatment for patients with ARDS given its anti-inflammatory and lung-protective effects.

Effectiveness and safety of awake prone positioning in COVID-19-related acute hypoxaemic respiratory failure: an overview of systematic reviews

ObjectiveTo evaluate and summarize systematic reviews of the effects and safety of awake prone positioning for COVID-19-related acute hypoxaemic respiratory failure.MethodsA comprehensive search was conducted on PubMed, Embase, the Cochrane Library, Web of Science, CNKI, CSPD, CCD and CBM from their inception to March 28, 2023. Systematic reviews (SRs) of awake prone positioning (APP) for COVID-19-related acute hypoxaemic respiratory failure in adults were included. Two reviewers screened the eligible articles, and four reviewers in pairs extracted data and assessed the methodological quality/certainty of the evidence of all included SRs by AMSTAR 2 and GRADE tools. The overlap of primary studies was measured by calculating corrected covered areas. Data from the included reviews were synthesized with a narrative description.ResultsA total of 11 SRs were included. The methodological quality of SRs included 1 “High”, 4 “Moderate”, 2 “Low” and 4 “Critically low” by AMSTAR 2. With the GRADE system, no high-quality evidence was found, and only 14 outcomes provided moderate-quality evidence. Data synthesis of the included SR outcomes showed that APP reduced the risk of requiring intubation (11 SRs) and improving oxygenation (3 SRs), whereas reduced significant mortality was not found in RCT-based SRs. No significant difference was observed in the incidence of adverse events between groups (8 SRs). The corrected covered area index was 27%, which shows very high overlap among studies.ConclusionThe available SRs suggest that APP has benefits in terms of reducing intubation rates and improving oxygenation for COVID-19-related acute hypoxemic respiratory failure, without an increased risk of adverse events. The conclusion should be treated with caution because of the generally low quality of methodology and evidence.Trial registrationThe protocol for this review was registered with PROSPERO: CRD42023400986. Registered 15 April 2023.

Use of airway pressure-based indices to detect high and low inspiratory effort during pressure support ventilation: a diagnostic accuracy study

BackgroundAssessment of the patient’s respiratory effort is essential during assisted ventilation. We aimed to evaluate the accuracy of airway pressure (Paw)-based indices to detect potential injurious inspiratory effort during pressure support (PS) ventilation.MethodsIn this prospective diagnostic accuracy study conducted in four ICUs in two academic hospitals, 28 adult acute respiratory failure patients undergoing PS ventilation were enrolled. A downward PS titration was conducted from 20 cmH2O to 2 cmH2O at a 2 cmH2O interval. By performing an end-expiratory airway occlusion maneuver, the negative Paw generated during the first 100 ms (P0.1) and the maximal negative swing of Paw (∆Pocc) were measured. After an end-inspiratory airway occlusion, Paw reached a plateau, and the magnitude of change in plateau from peak Paw was measured as pressure muscle index (PMI). Esophageal pressure was monitored and inspiratory muscle pressure (Pmus) and Pmus–time product per minute (PTPmus/min) were used as the reference standard for the patient’s effort. High and low effort was defined as Pmus > 10 and < 5 cmH2O, or PTPmus/min > 200 and < 50 cmH2O s min−1, respectively.ResultsA total of 246 levels of PS were tested. The low inspiratory effort was diagnosed in 145 (59.0%) and 136 (55.3%) PS levels using respective Pmus and PTPmus/min criterion. The receiver operating characteristic area of the three Paw-based indices by the respective two criteria ranged from 0.87 to 0.95, and balanced sensitivity (0.83–0.96), specificity (0.74–0.88), and positive (0.80–0.91) and negative predictive values (0.78–0.94) were obtained. The high effort was diagnosed in 34 (13.8%) and 17 (6.9%) support levels using Pmus and PTPmus/min criterion, respectively. High receiver operating characteristic areas of the three Paw-based indices by the two criteria were found (0.93–0.95). A high sensitivity (0.80–1.00) and negative predictive value (0.97–1.00) were found with a low positive predictive value (0.23–0.64).ConclusionsBy performing simple airway occlusion maneuvers, the Paw-based indices could be reliably used to detect low inspiratory efforts. Non-invasive and easily accessible characteristics support their potential bedside use for avoiding over-assistance. More evaluation of their performance is required in cohorts with high effort.

Pulmonary Surfactant in Adult ARDS: Current Perspectives and Future Directions.

Acute respiratory distress syndrome (ARDS) is a major cause of hypoxemic respiratory failure in adults, leading to the requirement for mechanical ventilation and poorer outcomes. Dysregulated surfactant metabolism and function are characteristic of ARDS. A combination of alveolar epithelial damage leading to altered surfactant synthesis, secretion, and breakdown with increased functional inhibition from overt alveolar inflammation contributes to the clinical features of poor alveolar compliance and alveolar collapse. Quantitative and qualitative alterations in the bronchoalveolar lavage and tracheal aspirate surfactant composition contribute to ARDS pathogenesis. Compared to neonatal respiratory distress syndrome (nRDS), replacement studies of exogenous surfactants in adult ARDS suggest no survival benefit. However, these studies are limited by disease heterogeneity, variations in surfactant preparations, doses, and delivery methods. More importantly, the lack of mechanistic understanding of the exact reasons for dysregulated surfactant remains a significant issue. Moreover, studies suggest an extremely short half-life of replaced surfactant, implying increased catabolism. Refining surfactant preparations and delivery methods with additional co-interventions to counteract surfactant inhibition and degradation has the potential to enhance the biophysical characteristics of surfactant in vivo.

Parallel Venovenous Extracorporeal Membrane Oxygenation Circuits for Refractory Hypoxemia in a Super-Super-Obese Patient

VENOVENOUS EXTRACORPOREAL MEMBRANE OXYGENATION (VV ECMO) represents a rescue form of life support for refractory respiratory failure, shown to confer a mortality benefit. 1 Zhu Y Zhang M Zhang R et al. Extracorporeal membrane oxygenation versus mechanical ventilation alone in adults with severe acute respiratory distress syndrome: A systematic review and meta-analysis. Int J Clin Pract. 2021; 75: e14046 Crossref PubMed Scopus (5) Google Scholar ,2 Peek GJ Mugford M Tiruvoipati R et al. Efficacy 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: 1351-1363 Abstract Full Text Full Text PDF PubMed Scopus (2409) Google Scholar Although relative contraindications to VV ECMO have been evolving with technology and experience, they currently include mechanical ventilation for >7 days (with plateau pressure [Pplat] >30 cmH2O and/or fraction of inspired oxygen [FiO2] >90%), intracranial hemorrhage or systemic bleeding, irreversible and incapacitating central nervous system pathology, immunosuppression, terminal malignancy, and advanced age. 3 Tonna JE Abrams D Brodie D et al. Management of adult patients supported with venovenous extracorporeal membrane oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO J. 2021; 67: 601-610 Crossref PubMed Scopus (114) Google Scholar The latest ECMO guidelines do not list obesity as a contraindication. 3 Tonna JE Abrams D Brodie D et al. Management of adult patients supported with venovenous extracorporeal membrane oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO). ASAIO J. 2021; 67: 601-610 Crossref PubMed Scopus (114) Google Scholar In fact, studies support the use of VV ECMO in patients with obesity in light of similar or even better survival outcomes compared to their nonobese counterparts. 4 Lazzeri C Bonizzoli M Cianchi G et al. Body mass index and echocardiography in refractory ARDS treated with veno-venous extracorporeal membrane oxygenation. J Artif Organs. 2017; 20: 50-56 Crossref PubMed Scopus (18) Google Scholar , 5 Swol J Buchwald D Dudda M et al. Veno-venous extracorporeal membrane oxygenation in obese surgical patients with hypercapnic lung failure. Acta Anaesthesiol Scand. 2014; 58: 534-538 Crossref PubMed Google Scholar , 6 Kon ZN Dahi S Evans CF et al. Class III obesity is not a contraindication to venovenous extracorporeal membrane oxygenation support. Ann Thorac Surg. 2015; 100: 1855-1860 Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar , 7 Al-Soufi S Buscher H Nguyen ND et al. Lack of association between body weight and mortality in patients on veno-venous extracorporeal membrane oxygenation. Intensive Care Med. 2013; 39: 1995-2002 Crossref PubMed Scopus (41) Google Scholar , 8 Zaidi SAA Saleem K. Obesity as a risk factor for failure to wean from ECMO: A systematic review and meta-analysis. Can Respir J. 2021; 20219967357 Crossref PubMed Scopus (5) Google Scholar , 9 Cho WH OH JY Yeo HJ et al. Obesity survival paradox in pneumonia supported with extracorporeal membrane oxygenation: Analysis of the national registry. J Crit Care. 2018; 48: 453-457 Crossref PubMed Scopus (15) Google Scholar , 10 Galvagno Jr., SM Pelekhaty S Cornachione CR et al. Does weight matter? Outcomes in adult patients on venovenous extracorporeal membrane oxygenation when stratified by obesity class. Anesth Analg. 2020; 131: 754-761 Crossref PubMed Scopus (24) Google Scholar However, skepticism still exists, especially for those with extreme body mass index (BMI), defined as super-obese (BMI >50) or super-super obese (BMI >60). Apart from practical challenges, such as cannulation and proning difficulties, the complex pulmonary and cardiovascular pathophysiology associated with extreme obesity carries the risk of inadequate ECMO flows for the body surface area (BSA), with resultant hypoxemia, as well as hemolysis with secondary coagulopathy from required high flows. The study authors report the successful implementation of 2 in-parallel VV ECMO circuits to overcome the limitations encountered in a super-super-obese patient undergoing conventional VV ECMO for refractory respiratory failure.

Highlights from the Respiratory Failure and Mechanical Ventilation 2022 Conference.

The Respiratory Intensive Care Assembly of the European Respiratory Society gathered in Berlin to organise the second Respiratory Failure and Mechanical Ventilation Conference in June 2022. The conference covered several key points of acute and chronic respiratory failure in adults. During the 3-day conference, ventilatory strategies, patient selection, diagnostic approaches, treatment and health-related quality of life topics were addressed by a panel of international experts. Lectures delivered during the event have been summarised by Early Career Members of the Assembly and take-home messages highlighted.

High-flow nasal cannula versus non-invasive ventilation for acute hypercapnic respiratory failure in adults: a systematic review and meta-analysis of randomized trials

BackgroundNon-invasive ventilation (NIV) with bi-level positive pressure ventilation is a first-line intervention for selected patients with acute hypercapnic respiratory failure. Compared to conventional oxygen therapy, NIV may reduce endotracheal intubation, death, and intensive care unit length of stay (LOS), but its use is often limited by patient tolerance and treatment failure. High-flow nasal cannula (HFNC) is a potential alternative treatment in this patient population and may be better tolerated.Research questionFor patients presenting with acute hypercapnic respiratory failure, is HFNC an effective alternative to NIV in reducing the need for intubation?MethodsWe searched EMBASE, MEDLINE, and the Cochrane library from database inception through to October 2021 for randomized clinical trials (RCT) of adults with acute hypercapnic respiratory failure assigned to receive HFNC or NIV. The Cochrane risk-of-bias tool for randomized trials was used to assess risk of bias. We calculated pooled relative risks (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with corresponding 95% confidence intervals (CI) using a random-effects model.ResultsWe included eight RCTs (n = 528) in the final analysis. The use of HFNC compared to NIV did not reduce the risk of our primary outcome of mortality (RR 0.86, 95% CI 0.48–1.56, low certainty), or our secondary outcomes including endotracheal intubation (RR 0.80, 95% CI 0.46–1.39, low certainty), or hospital LOS (MD − 0.82 days, 95% CI − 1.83–0.20, high certainty). There was no difference in change in partial pressure of carbon dioxide between groups (MD − 1.87 mmHg, 95% CI − 5.34–1.60, moderate certainty).InterpretationThe current body of evidence is limited in determining whether HFNC may be either superior, inferior, or equivalent to NIV for patients with acute hypercapnic respiratory failure given imprecision and study heterogeneity. Further studies are needed to better understand the effect of HFNC on this population.

Epithelial Endoplasmic Reticulum Stress Enhances the Risk of Muc5b-associated Lung Fibrosis.

The gain-of-function minor allele of the MUC5B (mucin 5B, oligomeric mucus/gel-forming) promoter (rs35705950) is the strongest risk factor for idiopathic pulmonary fibrosis (IPF), a devastating fibrotic lung disease that leads to progressive respiratory failure in adults. We have previously demonstrated that Muc5b overexpression in mice worsens lung fibrosis after bleomycin exposure and have hypothesized that excess Muc5b promotes endoplasmic reticulum (ER) stress and apoptosis, stimulating fibrotic lung injury. Here, we report that ER stress pathway members ATF4 (activating transcription factor 4) and ATF6 coexpress with MUC5B in epithelia of the distal IPF airway and honeycomb cyst and that this is more pronounced in carriers of the gain-of-function MUC5B promoter variant. Similarly, in mice exposed to bleomycin, Muc5b expression is temporally associated with markers of ER stress. Using bulk and single-cell RNA sequencing in bleomycin-exposed mice, we found that pathologic ER stress-associated transcripts Atf4 and Ddit3 (DNA damage inducible transcript 3) were elevated in alveolar epithelia of SFTPC-Muc5b transgenic (SFTPC-Muc5bTg) mice relative to wild-type (WT) mice. Activation of the ER stress response inhibits protein translation for most genes by phosphorylation of Eif2α (eukaryotic translation initiation factor 2 alpha), which prevents guanine exchange by Eif2B and facilitates translation of Atf4. The integrated stress response inhibitor (ISRIB) facilitates interaction of phosphorylated Eif2α with Eif2B, overcoming translation inhibition associated with ER stress and reducing Atf4. We found that a single dose of ISRIB diminished Atf4 translation in SFTPC-Muc5bTg mice after bleomycin injury. Moreover, ISRIB resolved the exaggerated fibrotic response of SFTPC-Muc5bTg mice to bleomycin. In summary, we demonstrate that MUC5B and Muc5b expression is associated with pathologic ER stress and that restoration of normal translation with a single dose of ISRIB promotes lung repair in bleomycin-injured Muc5b-overexpressing mice.

Treatment of acute respiratory failure: extracorporeal membrane oxygenation

Background: Extracorporeal membrane oxygenation (ECMO) support for tissue oxygenation can improve the survival of patients with life-threatening respiratory distress syndrome or cardiac failure.Current Concepts: Recently, the use of ECMO in acute respiratory distress syndrome has first been reported by a multicenter randomized controlled trial, known as the conventional ventilation or ECMO for severe adult respiratory failure trial. The ECMO application is dramatically increasing with the increasing number of patients experiencing acute respiratory failure due to coronavirus disease 2019 pneumonia. In this review, we explain the indications of the ECMO application and ECMO-associated complications.Discussion and Conclusion: The ECMO application in lung diseases, such as coronavirus disease 2019 and acute respiratory distress syndrome, has significant outcomes in securing the treatment periods and reducing mortality. Therefore, accumulating knowledge and experience in the ECMO application can produce positive outcomes.

Impact of COVID-19 on vascular patients worldwide: analysis of the COVIDSurg data.

The COVIDSurg collaborative was an international multicenter prospective analysis of perioperative data from 235 hospitals in 24 countries. It found that perioperative COVID-19 infection was associated with a mortality rate of 24%. At the same time, the COVER study demonstrated similarly high perioperative mortality rates in vascular surgical patients undergoing vascular interventions even without COVID-19, likely associated with the high burden of comorbidity associated with vascular patients. This is a vascular subgroup analysis of the COVIDSurg cohort. All patients with a suspected or confirmed diagnosis of COVID-19 in the 7 days prior to, or in the 30 days following a vascular procedure were included. The primary outcome was 30-day mortality. Secondary outcomes were pulmonary complications (adult respiratory distress syndrome, pulmonary embolism, pneumonia and respiratory failure). Logistic regression was undertaken for dichotomous outcomes. Overall, 602 patients were included in this subgroup analysis, of which 88.4% were emergencies. The most common operations performed were for vascular-related dialysis access procedures (20.1%, N.=121). The combined 30-day mortality rate was 27.2%. Composite secondary pulmonary outcomes occurred in half of the vascular patients (N.=275, 45.7%). Mortality following vascular surgery in COVID positive patients was significantly higher than levels reported pre-pandemic, and similar to that seen in other specialties in the COVIDSurg cohort. Initiatives and surgical pathways that ensure vascular patients are protected from exposure to COVID-19 in the peri-operative period are vital to protect against excess mortality.

Outcomes From Long-Distance Interfacility Transport of Adult Patients on Acute Mechanical Circulatory Support

Cardiac and respiratory failure in adults has historically had very high mortality. Mechanical circulatory support (MCS) has shown promise to improve outcomes for these patients; however, only tertiary care centers typically have the critical care resources to manage patients on MCS. We investigated to see if we could provide safe, long-distance transport of MCS-supported patients to our tertiary center after MCS is initiated at community or regional hospitals. We also investigated if we could provide this service without using physicians or perfusionists for the en route management of MCS devices. Our outcome results, based on survival to discharge, are comparable with other published survival outcomes data for this patient population, suggesting that patients on MCS devices can be safely transported by air and ground without incurring additional mortality risk. Additionally, instead of perfusionists or physicians, specially trained nurses were used to manage all MCS devices en route. This change to the typical transport team structure has the potential to make the transport of MCS-supported patients more cost-effective for health care systems nationwide.

Long-term outcomes of adults with acute respiratory failure treated with veno-venous extracorporeal membrane oxygenation.

Veno-venous extracorporeal membrane oxygenation is increasingly used for severe but potentially reversible acute respiratory failure in adults; however, there are limited data regarding long-term morbidity. At our institution, most patients requiring veno-venous extracorporeal membrane oxygenation have been followed up by a single physician. Our primary aim was to describe the serial long-term morbidity for respiratory, musculoskeletal and psychological functioning. A retrospective audit of inpatient and outpatient medical records was conducted. A total of 125 patients treated with veno-venous extracorporeal membrane oxygenation for primary respiratory failure were included. The patients were young (mean (standard deviation) age 43.7 (4.1) years), obese (mean (standard deviation) body mass index 30.8 (10.4) kg/m2), and mostly were male (59%). Most patients (60%) had no comorbidities. The survival rate to discharge was 70%, with body mass index and the number of comorbidities being independent predictors of survival on multiple logistic regression analysis. Over half (57%) of the Australian survivors had regular outpatient follow-up. They had a median of three reviews (range 1–9) over a median of 11.8 months (range 1.5-79) months. Breathlessness and weakness resolved in most within six months, with lung function abnormalities taking longer to resolve. Over half (60%) returned to employment within six months of discharge. Over a quarter (29%) displayed symptoms of anxiety, depression or post-traumatic stress disorder.

Contraindications to the Initiation of Veno-Venous ECMO for Severe Acute Respiratory Failure in Adults: A Systematic Review and Practical Approach Based on the Current Literature.

(1) Background: Extracorporeal membrane oxygenation (ECMO) is increasingly used for acute respiratory failure with few absolute but many relative contraindications. The provider in charge often has a difficult time weighing indications and contraindications to anticipate if the patient will benefit from this treatment, a decision that often decides life and death for the patient. To assist in this process in coming to a good evidence-based decision, we reviewed the available literature. (2) Methods: We performed a systematic review through a literature search of the MEDLINE database of former and current absolute and relative contraindications to the initiation of ECMO treatment. (3) Results: The following relative and absolute contraindications were identified in the literature: absolute—refusal of the use of extracorporeal techniques by the patient, advanced stage of cancer, fatal intracerebral hemorrhage/cerebral herniation/intractable intracranial hypertension, irreversible destruction of the lung parenchyma without the possibility of transplantation, and contraindications to lung transplantation; relative—advanced age, immunosuppressed patients/pharmacological immunosuppression, injurious ventilator settings > 7 days, right-heart failure, hematologic malignancies, especially bone marrow transplantation and graft-versus-host disease, SAPS II score ≥ 60 points, SOFA score > 12 points, PRESERVE score ≥ 5 points, RESP score ≤ −2 points, PRESET score ≥ 6 points, and “do not attempt resuscitation” order (DN(A)R status). (4) Conclusions: We provide a simple-to-follow algorithm that incorporates absolute and relative contraindications to the initiation of ECMO treatment. This algorithm attempts to weigh pros and cons regarding the benefit for an individual patient and hopefully assists caregivers to make better, informed decisions.

High flow nasal cannula for adult acute hypoxemic respiratory failure in the ED setting.

IntroductionHigh flow nasal cannula (HFNC) is a noninvasive ventilation (NIV) system that has demonstrated promise in the emergency department (ED) setting.ObjectiveThis narrative review evaluates the utility of HFNC in adult patients with acute hypoxemic respiratory failure in the ED setting.DiscussionHFNC provides warm (37 °C), humidified (100% relative humidity) oxygen at high flows with a reliable fraction of inspired oxygen (FiO2). HFNC can improve oxygenation, reduce airway resistance, provide humidified flow that can flush anatomical dead space, and provide a low amount of positive end expiratory pressure. Recent literature has demonstrated efficacy in acute hypoxemic respiratory failure, including pneumonia, acute respiratory distress syndrome (ARDS), coronavirus disease 2019 (COVID-19), interstitial lung disease, immunocompromised states, the peri-intubation state, and palliative care, with reduced need for intubation, length of stay, and mortality in some of these conditions. Individual patient factors play an important role in infection control risks with respect to the use of HFNC in patients with COVID-19. Appropriate personal protective equipment, adherence to hand hygiene, surgical mask placement over the HFNC device, and environmental controls promoting adequate room ventilation are the foundation for protecting healthcare personnel. Frequent reassessment of the patient placed on HFNC is necessary; those with severe end organ dysfunction, thoracoabdominal asynchrony, significantly increased respiratory rate, poor oxygenation despite HFNC, and tachycardia are at increased risk of HFNC failure and need for further intervention.ConclusionsHFNC demonstrates promise in several conditions requiring respiratory support. Further randomized trials are needed in the ED setting.

Management of Adult Patients Supported with Venovenous Extracorporeal Membrane Oxygenation (VV ECMO): Guideline from the Extracorporeal Life Support Organization (ELSO).

Disclaimer: The use of venovenous extracorporeal membrane oxygenation (VV ECMO) in adults has rapidly increased worldwide. This ELSO guideline is intended to be a practical guide to patient selection, initiation, cannulation, management, and weaning of VV ECMO for adult respiratory failure. This is a consensus document which has been updated from the previous version to provide guidance to the clinician.