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Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases. Computed tomography of the chest demonstrated bilateral lower lobe atelectasis. Heart catheterization and endomyocardial biopsy were unremarkable. Electromyogram (EMG) and nerve conduction studies (NCS) of the limb muscles revealed mild diffuse myopathy, normal sensory nerve conductions, and low-amplitude motor responses. Subsequent diaphragmatic EMG and NCS demonstrated severe myopathy. ICI-mediated myopathy predominantly affecting diaphragmatic muscles was diagnosed. Treatment included intravenous methylprednisolone, infliximab, abatacept, rituximab, and plasmapheresis. He underwent tracheostomy placement on hospital day 11 due to minimal improvement. He was discharged to a long-term acute care hospital, but unfortunately, he died less than 1 month later due to recurrent infections. irAEs can affect any organ system, but diaphragmatic dysfunction is uncommon. Use of diaphragmatic EMG, NCS, ultrasound study, or biopsy can support the diagnosis. Treatment includes systemic steroids, plasmapheresis, immunosuppressive medications, respiratory support, and cessation of causative medications. ICI-related diaphragmatic dysfunction should be suspected in those patients at risk with hypoxia, hypercapnia, or prolonged invasive or noninvasive ventilation without a distinct etiology. This case report exemplifies the importance of multidisciplinary workup and management of respiratory symptoms and insufficiency to identify and ameliorate irAEs. Diaphragmatic involvement can be associated with significant morbidity and mortality despite early aggressive multimodal therapy.

Immune-related adverse events (irAEs) have become increasingly prevalent with immune checkpoint inhibitor (ICI) cancer treatment. We present a 79-year-old man with metastatic renal cell carcinoma who developed shortness of breath and hypercapnic respiratory insufficiency after his first cycle of nivolumab and ipilimumab. Laboratory data showed elevated creatinine kinase, troponins, and transaminases. Computed tomography of the chest demonstrated bilateral lower lobe atelectasis. Heart catheterization and endomyocardial biopsy were unremarkable. Electromyogram (EMG) and nerve conduction studies (NCS) of the limb muscles revealed mild diffuse myopathy, normal sensory nerve conductions, and low-amplitude motor responses. Subsequent diaphragmatic EMG and NCS demonstrated severe myopathy. ICI-mediated myopathy predominantly affecting diaphragmatic muscles was diagnosed. Treatment included intravenous methylprednisolone, infliximab, abatacept, rituximab, and plasmapheresis. He underwent tracheostomy placement on hospital day 11 due to minimal improvement. He was discharged to a long-term acute care hospital, but unfortunately, he died less than 1 month later due to recurrent infections. irAEs can affect any organ system, but diaphragmatic dysfunction is uncommon. Use of diaphragmatic EMG, NCS, ultrasound study, or biopsy can support the diagnosis. Treatment includes systemic steroids, plasmapheresis, immunosuppressive medications, respiratory support, and cessation of causative medications. ICI-related diaphragmatic dysfunction should be suspected in those patients at risk with hypoxia, hypercapnia, or prolonged invasive or noninvasive ventilation without a distinct etiology. This case report exemplifies the importance of multidisciplinary workup and management of respiratory symptoms and insufficiency to identify and ameliorate irAEs. Diaphragmatic involvement can be associated with significant morbidity and mortality despite early aggressive multimodal therapy. [ABSTRACT FROM AUTHOR]

Systemic steroids are frequently used in critically ill patients for their anti-inflammatory properties. Potential benefits of these agents should be balanced against their known side effects. In this paper, we review trials assessing the use of systemic steroids in common conditions requiring admission to the intensive care unit. These include septic shock, the acute respiratory distress syndrome, severe pneumonia, COVID-19, and hypercapnic respiratory failure due to chronic obstructive pulmonary disease. We will mainly focus on well-conducted randomized controlled trials to determine whether steroids should be administered to critically ill patients presenting with these conditions. [ABSTRACT FROM AUTHOR]

Zihan Zhou,1,2,* Yuhui Wang,2,3,* Yongsheng Wang,1,2 Bo Yang,4 Chuchu Xu,1,2 Shuqin Wang,1,2 Wanchun Yang1,2 1Department of Respiratory and Critical Care Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei, Anhui, 230011, People’s Republic of China; 2The Fifth Clinical College of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China; 3Department of Cardiology, Hefei Hospital Affiliated to Anhui Medical University, Hefei, The Second People’s Hospital of Hefei, Hefei, Anhui, 230011, People’s Republic of China; 4Affiliated Hospital of West Anhui Health Vocational College, The Second People’s Hospital of Lu’an City, Lu’an, 237005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wanchun Yang, Department of Respiratory and Critical Care Medicine, Hefei Hospital Affiliated to Anhui Medical University, The Second People’s Hospital of Hefei, Hefei, Anhui, 230011, People’s Republic of China, Email hfey2023@163.comPurpose: To develop and validate a nomogram for assessing the risk of developing hypercapnic respiratory failure (HRF) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Patients and Methods: From January 2019 to August 2023, a total of 334 AECOPD patients were enrolled in this research. We employed the Least Absolute Shrinkage and Selection Operator (LASSO) regression and multivariate logistic regression to determine independent predictors and develop a nomogram. This nomogram was appraised by the area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer–Lemeshow goodness-of-fit test (HL test), decision curve analysis (DCA), and clinical impact curve (CIC). The enhanced bootstrap method was used for internal validation.Results: Sex, prognostic nutritional index (PNI), hematocrit (HCT), and activities of daily living (ADL) were independent predictors of HRF in AECOPD patients. The developed nomogram based on the above predictors showed good performance. The AUCs for the training, internal, and external validation cohorts were 0.841, 0.884, and 0.852, respectively. The calibration curves and HL test showed excellent concordance. The DCA and CIC showed excellent clinical usefulness. Finally, a dynamic nomogram was developed (https://a18895635453.shinyapps.io/dynnomapp/).Conclusion: This nomogram based on sex, PNI, HCT, and ADL demonstrated high accuracy and clinical value in predicting HRF. It is a less expensive and more accessible approach to assess the risk of developing HRF in AECOPD patients, which is more suitable for primary hospitals, especially in developing countries with high COPD-related morbidity and mortality.Keywords: acute exacerbation of chronic obstructive pulmonary disease, hypercapnic respiratory failure, nomogram, prediction model

Background. Acute respiratory failure is a prevalent condition in childhood with a high rate of mortality. Invasive mechanical ventilation support may be required for the management of these patients. Extracorporeal membrane oxygenation (ECMO) is a method used when ventilation support is insufficient. However, the less invasive extracorporeal carbon dioxide removal method can be used as an alternative in cases of hypercapnic respiratory failure. Case. A 9-year-old patient with cystic fibrosis presented to the hospital with acute respiratory failure due to pneumonia. Bilateral patchy areas of consolidation were evident in the chest x-ray. Invasive mechanical ventilation support was consequently provided to treat severe hypercapnia. Although peak and plateau pressure levels exceeded 32 cmH2O (49 cmH2O) and 28 cmH2O (35 cmH2O), respectively, the patient continued to have severe respiratory acidosis. Therefore extracorporeal carbon dioxide removal support was initiated to provide lung-protective ventilation. By Day 10, venovenous ECMO support was initiated due to deteriorating oxygenation. Conclusion. In cases where conventional invasive mechanical ventilation support is insufficient due to acute hypercapnic respiratory failure, extracorporeal carbon dioxide removal support, which is less invasive compared to ECMO, should be considered as an effective and reliable alternative method. However, it should be noted that extracorporeal carbon dioxide removal support does not affect oxygenation; it functions solely as a carbon dioxide removal system. [ABSTRACT FROM AUTHOR]

Non-thyroidal illness syndrome (NTIS) is often observed in critically ill patients. This study aimed to examine thyroid hormone changes in patients with chronic obstructive pulmonary disease (COPD) experiencing acute hypercapnic respiratory failure (AHRF) and to evaluate the impact of these alterations on clinical outcomes.

Abstract Objective There are no population-based data on the relative importance of specific causes of hypercapnic respiratory failure (HRF). We sought to quantify the associations between hospitalisation with HRF and potential antecedent causes including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and congestive cardiac failure. We used data on the prevalence of these conditions to estimate the population attributable fraction for each cause. Methods A case–control study was conducted among residents aged ≥ 40 years from the Liverpool local government area in Sydney, Australia. Cases were identified from hospital records based on PaCO2 > 45 mmHg. Controls were randomly selected from the study population using a cluster sampling design. We collected self-reported data on medication use and performed spirometry, limited-channel sleep studies, venous sampling for N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and sniff nasal inspiratory pressure (SNIP) measurements. Logistic regression analyses were performed using directed acyclic graphs to identify covariates. Results We recruited 42 cases and 105 controls. HRF was strongly associated with post-bronchodilator airflow obstruction, elevated NT-proBNP levels, reduced SNIP measurements and self-reported opioid medication use. There were no differences in the apnoea-hypopnea index or oxygen desaturation index between groups. COPD had the highest population attributable fraction (42%, 95% confidence interval 18% to 59%). Conclusions COPD, congestive cardiac failure, and self-reported use of opioid medications, but not obstructive sleep apnea, are important causes of HRF among adults over 40 years old. No single cause accounts for the majority of cases based on the population attributable fraction.

This state-of-the-art review provides an overview of the history of home mechanical ventilation (HMV), including early descriptions of mechanical ventilation from ancient and Renaissance perspectives and the mass development of ventilators designed for long-term use during the poliomyelitis epidemic. Seminal data from key clinical trials supports the application of HMV in certain patients with chronic obstructive pulmonary disease, neuromuscular disease and obesity-related respiratory failure. Innovative engineering coupled with refined physiological understanding now permits widespread delivery of home mechanical ventilation to a global population, using portable devices with advanced ventilatory modes and telemonitoring capabilities. Exponential growth in digital technology continues, and ongoing research is needed to understand how to harness clinical and physiological data to benefit patients and healthcare services in a clinically- and cost-effective manner. [ABSTRACT FROM AUTHOR]

This document summarizes the work of the COPD Technical Expert Panel working group. For patients with COPD, the most pressing current coverage barriers identified were onerous diagnostic requirements focused on oxygenation (rather than ventilation) and difficulty obtaining bilevel devices with backup rate capabilities. Because of these difficulties, many patients with COPD were instead sometimes prescribed home mechanical ventilators. Critical evidence supports changes to current policies, including randomized controlled trial evidence suggesting a mortality benefit from bilevel positive airway pressure with backup rate and updated clinical practice guidelines from the American Thoracic Society as well as the European Respiratory Society. To achieve optimal access to noninvasive ventilation for patients with COPD, we make the following key recommendations: (1) removal of the need for overnight oximetry testing; (2) the ability to initiate therapy using bilevel devices with backup rate capability; and (3) increased duration of time to meet adherence criteria (ie, a second 90-day trial period) in those patients actively engaged in their care. Clear guidelines based on medical necessity are also included for patients who require initiation of or switch to a home mechanical ventilator. Adoption of these proposed recommendations would result in the right device, for the right type of patient with COPD, at the right time. Finally, we emphasize the need for adequate clinical support during initiation and maintenance of home noninvasive ventilation in such patients.

Abstract Background Decannulation is an essential step in liberating tracheostomised patients from mechanical ventilation. There is a paucity of literature on tracheostomy decannulation methods and procedures, leaving the decision to expert opinion and institutional guidelines. Failure to decannulate may result from several reasons, such as severe dysphagia, retention of copious secretions requiring invasive airway clearing techniques, or tracheal stenosis. Meanwhile, the combined use of either non-invasive ventilation during bronchoscopy has been reported as a successful strategy in different diagnostic and therapeutic clinical conditions. Case presentation We describe a patient admitted to the intensive care unit due to respiratory failure after a decannulation process and the use of non-invasive ventilation as rescue therapy during urgent flexible bronchoscopy to support this procedure and control acute hypercapnic respiratory failure and avoid recannulation process. Conclusions This case presents the rationale approach of using non-invasive ventilation during bronchoscopy to avoid decannulation failure by accumulation of secretions during this procedure.

Objective: There are no population-based data on the relative importance of specific causes of hypercapnic respiratory failure (HRF). We sought to quantify the associations between hospitalisation with HRF and potential antecedent causes including chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and congestive cardiac failure. We used data on the prevalence of these conditions to estimate the population attributable fraction for each cause. Methods: A case–control study was conducted among residents aged ≥ 40 years from the Liverpool local government area in Sydney, Australia. Cases were identified from hospital records based on PaCO2 > 45 mmHg. Controls were randomly selected from the study population using a cluster sampling design. We collected self-reported data on medication use and performed spirometry, limited-channel sleep studies, venous sampling for N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, and sniff nasal inspiratory pressure (SNIP) measurements. Logistic regression analyses were performed using directed acyclic graphs to identify covariates. Results: We recruited 42 cases and 105 controls. HRF was strongly associated with post-bronchodilator airflow obstruction, elevated NT-proBNP levels, reduced SNIP measurements and self-reported opioid medication use. There were no differences in the apnoea-hypopnea index or oxygen desaturation index between groups. COPD had the highest population attributable fraction (42%, 95% confidence interval 18% to 59%). Conclusions: COPD, congestive cardiac failure, and self-reported use of opioid medications, but not obstructive sleep apnea, are important causes of HRF among adults over 40 years old. No single cause accounts for the majority of cases based on the population attributable fraction. [ABSTRACT FROM AUTHOR]

Introduction: Although the benefit of non-invasive mechanical ventilation (NIMV) has been proven in the management of acute exacerbations of chronic obstructive pulmonary disease (COPD), the data are limited for other lung conditions, including pneumonia and bronchiectasis. In this study, we aimed to investigate the success of NIMV in COPD patients with acute hypercapnic respiratory failure (AHRF) and concomitant pneumonia or bronchiectasis. Methods: Among the patients hospitalized in the intensive care unit (ICU) due to AHRF, 62 patients suitable for NIMV application were included in the study. The patients were divided into three groups: Group 1: COPD (n=34), Group 2: COPD + bronchiectasis (n=11), and Group 3: COPD + pneumonia (n=17). We evaluated the success of NIMV among those 3 groups. Results: Three study groups were similar for NIMV success, length of stay in ICU, and mortality. Discussion and Conclusion: There is increasing evidence for the benefit of NIMV in the management of AHRF. Although the use of NIMV in COPD exacerbations has been strongly recommended by many randomized controlled trials, more studies are needed to prove its benefit in patients with pneumonia and bronchiectasis. [ABSTRACT FROM AUTHOR]

Background: Noninvasive ventilation (NIV) is used for patients with chronic obstructive pulmonary disease (COPD) and chronic hypercapnia. However, evidence for clinical efficacy and optimal management of therapy is limited.Target Audience: Patients with COPD, clinicians who care for them, and policy makers.Methods: We summarized evidence addressing five PICO (patients, intervention, comparator, and outcome) questions. The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach was used to evaluate the certainty in evidence and generate actionable recommendations. Recommendations were formulated by a panel of pulmonary and sleep physicians, respiratory therapists, and methodologists using the Evidence-to-Decision framework.Recommendations: 1) We suggest the use of nocturnal NIV in addition to usual care for patients with chronic stable hypercapnic COPD (conditional recommendation, moderate certainty); 2) we suggest that patients with chronic stable hypercapnic COPD undergo screening for obstructive sleep apnea before initiation of long-term NIV (conditional recommendation, very low certainty); 3) we suggest not initiating long-term NIV during an admission for acute-on-chronic hypercapnic respiratory failure, favoring instead reassessment for NIV at 2-4 weeks after resolution (conditional recommendation, low certainty); 4) we suggest not using an in-laboratory overnight polysomnogram to titrate NIV in patients with chronic stable hypercapnic COPD who are initiating NIV (conditional recommendation, very low certainty); and 5) we suggest NIV with targeted normalization of PaCO2 in patients with hypercapnic COPD on long-term NIV (conditional recommendation, low certainty).Conclusions: This expert panel provides evidence-based recommendations addressing the use of NIV in patients with COPD and chronic stable hypercapnic respiratory failure.

Cuiping Xu, Feng Yang, Qimin Wang, Wei Gao Department of Respiratory and Critical Care Medicine, China Rehabilitation Research Center, Rehabilitation School of Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Wei Gao, Tel +86 10-87569070, Fax +86 10-67573428, Email rhhuxi@163.comPurpose: We aimed to evaluate whether high flow nasal cannula (HFNC) is an effective and safe method for adult patients with acute hypercapnic respiratory failure (AHRF).Methods: We searched the Cochrane Library, Embase, and PubMed databases from inception to August 2022 to obtain randomized controlled trials (RCTs) that compared HFNC with conventional oxygen treatment (COT) or non-invasive ventilation (NIV) in patients with AHRF, and then performed a meta-analysis.Results: A total of ten parallel RCTs with 1265 individuals were identified. Of them, two studies compared HFNC with COT and eight studies compared HFNC with NIV. In terms of intubation rate, mortality, and arterial blood gas (ABG) improvement, HFNC showed comparable effects to NIV and COT. However, HFNC was more comfortable (mean difference [MD] − 1.87, 95% confidence interval [CI] =− 2.59, − 1.15, P < 0.00001, I2 =0%) and resulted in fewer adverse events (odds ratio [OR] 0.12, 95% CI=0.06, 0.28, P< 0.00001, I2 = 0%), compared with NIV. In comparison to NIV, HFNC could significantly lower heart rate (HR) (MD − 4.66, 95% CI=− 6.82, − 2.50, P < 0.0001, I2 =0%), respiratory rate (RR) (MD − 1.17, 95% CI=− 2.03, − 0.31, P =0.008, I2 =0%), and hospital stay length (MD − 0.80, 95% CI=− 1.44, − 0.16, P =0.01, I2 =0%). NIV showed a decreased frequency in the treatment crossover rate, compared with HFNC in patients with pH< 7.30 (OR 5.78, 95% CI=1.50, 22.31, P = 0.01, I2: not applicable). Contrary to COT, HFNC could considerably reduce the need for NIV (OR 0.57, 95% CI=0.35, 0.91, P=0.02, I2=0%).Conclusion: HFNC was effective and safe in patients with AHRF. However, in patients with pH < 7.30, HFNC may result in a higher incidence of treatment crossover, compared with NIV. Compared to COT, HFNC may decrease the need for NIV in patients with compensated hypercapnia.Keywords: high-flow nasal cannula, non-invasive ventilation, conventional oxygen treatment, hypercapnic respiratory failure

Dear Editor, The recent study published by Purohit et al. provides new evidence on the safety of immediate withdrawal of non-invasive ventilation (NIV) in chronic obstructive pulmonary disease (COPD) patients admitted with acute hypercapnic respiratory failure (AHRF) after recovery...

COPD is a progressive inflammatory process affecting both the airways and alveolar structures of the lungs. Exacerbations of COPD are episodes of acute worsening of this inflammatory process, often triggered by infections. The most severe exacerbations are characterized by substantial air trapping and inspiratory muscle overload, which leads to hypercapnic respiratory failure. Pharmacologic therapies focus on intense bronchodilator administration (usually by aerosol), corticosteroids, and antibiotics. Respiratory life support technologies are often needed for severe exacerbations and range from carefully titrated supplemental O2 administration to positive-pressure ventilation (both invasive and noninvasive). Future life support strategies will likely involve extracorporeal life support technologies. [ABSTRACT FROM AUTHOR]

Dear Editor, The recent study published by Ketan et al. provides emerging evidence on the expanding indications for high-flow nasal oxygen (HFNO) therapy in chronic obstructive pulmonary disease (COPD). The indications for hypoxemic respiratory failure being robust, the indications of hypercapnic respiratory failure are emerging....

Abstract Background Non-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 question For patients presenting with acute hypercapnic respiratory failure, is HFNC an effective alternative to NIV in reducing the need for intubation? Methods We 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. Results We 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). Interpretation The 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.

Thyroid cancer is a type of malignancy that is considered to have a low morbidity and an indolent disease course in most patients. Though some of its pathologic variants such as anaplastic carcinoma may present with advanced disease staging, it is important to consider the possibility of metastasis to thyroid which may present like a thyroid primary. Solid organ carcinomas form the bulk of the uncommon metastasis to the thyroid, though sarcomas from various organs also rarely exhibit this activity. Literature demonstrating sound diagnostic criteria for these occurrences is sparse. We present a case of uterine sarcoma with distant metastasis to the thyroid gland that initially presented as hypercapnic respiratory failure. Only an inpatient episode of uterine bleeding prompted our team to explore the potential of a metastatic process. Our diagnosis was made utilizing a multidisciplinary approach that we feel is important for clinicians dealing with metastatic disease to the thyroid. In addition to sound physical exam, and use of appropriate imaging modality, we feel it is essential to utilize a detailed cytohistologic specimen evaluation, immunohistochemistry, and genetic sequencing to effectively work up such patients. Although our patient did not survive her hospital stay, we hope this paper brings greater awareness of this malignancy and acts as a benchmark for diagnosing such an unusual remote primary.

Background: Decannulation is an essential step in liberating tracheostomised patients from mechanical ventilation. There is a paucity of literature on tracheostomy decannulation methods and procedures, leaving the decision to expert opinion and institutional guidelines. Failure to decannulate may result from several reasons, such as severe dysphagia, retention of copious secretions requiring invasive airway clearing techniques, or tracheal stenosis. Meanwhile, the combined use of either non-invasive ventilation during bronchoscopy has been reported as a successful strategy in different diagnostic and therapeutic clinical conditions. Case presentation: We describe a patient admitted to the intensive care unit due to respiratory failure after a decannulation process and the use of non-invasive ventilation as rescue therapy during urgent flexible bronchoscopy to support this procedure and control acute hypercapnic respiratory failure and avoid recannulation process. Conclusions: This case presents the rationale approach of using non-invasive ventilation during bronchoscopy to avoid decannulation failure by accumulation of secretions during this procedure. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal carbon dioxide removal (ECCO2R) was used to prevent invasive mechanical ventilation and associated mechanical damage in patients with acute respiratory distress syndrome (ARDS). Objectives: This study aimed to investigate the efficacy and safety of ECCO2R treatment in patients with ARDS or chronic obstructive pulmonary disease (COPD). Methods: MEDLINE, EMBASE, and the Cochrane Library were systematically searched for relevant studies that reported patient prognosis, blood gas parameters, and ECCO2R-related adverse events (AEs) published as of September 2020. Odds ratios (ORs), weighted mean differences (WMDs), and their corresponding 95% confidence intervals (CIs) were used to compare the outcomes. Results: Fifteen studies involving 532 ARDS or COPD patients were included. Compared with controls, ECCO2R did not influence the 28-day mortality (OR = 0.73, 95% CI: 0.28–1.87, p = 0.51), the length of hospital stay (WMD = 3.34, 95% CI: −5.22 to 11.90, p = 0.444), and the length of intensive care unit stay (WMD = −0.39, 95% CI: −8.76 to 7.99, p = 0.928). Compared with baseline values, partial pressure of carbon dioxide (PaCO2) in the ECCO2R group was significantly reduced, while the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) and pH increased. The overall rate of ECCO2R-related AEs was 35% (95% CI: 17–53%, p < 0.001), and bleeding was the most common AE with a rate of 22% (95% CI: 13–31%, p = 0.002). The rate of ECCO2R-related deaths was low. Conclusions: In conclusion, there was no statistically significant difference in the prognosis of patients with and without ECCO2R treatment. ECCO2R significantly reduced PaCO2 and improved PaO2/FiO2 and pH values in patients with ARDS or COPD. Bleeding was the most common ECCO2R-related AE. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients hospitalized for COPD exacerbation have an increased risk of mortality, particularly among those who fail bi-level positive airway pressure (BPAP) for hypercapnic respiratory failure subsequently requiring invasive mechanical ventilation. Therefore, we sought to investigate the treatment course of BPAP and factors associated with BPAP treatment failure. METHODS: We performed a retrospective cohort study using real-world evidence to investigate subjects with COPD who were treated with BPAP during a hospitalization for COPD exacerbation. Treatment outcomes were defined within 7 d from BPAP initiation as either failure, persistent, or success. Failure was defined as death or progression to invasive ventilation. Persistent was defined as receiving BPAP during hospital day 7. Success was defined as liberation from BPAP prior to hospital day 7 and not meeting criteria for failure. Unadjusted multinomial logistic regression models were used to examine the association between BPAP treatment outcomes and 17 recipient characteristics. RESULTS: Among the 427 clinical encounters, 78% were successful, 10% were persistent, and 12% experienced failure. The median time to failure and success was 8 h and 16 h, respectively. Increasing age, body mass index (BMI), bicarbonate level, and creatinine level were significantly associated with either BPAP treatment failure, persistent treatment, or both. CONCLUSIONS: The first 8 h following initiation of BPAP is a critical time period where patients are at high risk for life-threatening decompensation. Careful consideration should be given to increasing age, BMI, bicarbonate level, and creatinine level as these factors were associated with BPAP treatment failure or persistent treatment. [ABSTRACT FROM AUTHOR]

Abstract Background Non-invasive ventilation (NIV) is a recommended treatment for COPD patients suffering from chronic hypercapnic respiratory failure. Prolonged dyspnea after mask removal in the morning, often referred to as deventilation syndrome, is a common side effect but has been poorly characterized yet. This study aimed to explore the pathomechanism, identify risk factors and possible treatment strategies for the deventilation syndrome. Methods A prospective, controlled, non-blinded study was conducted. After a night with established NIV therapy, the patients underwent spirometry, blood gas analyses and 6-min walking tests (6MWT) directly, at 2 and 4 h after mask removal. Dyspnea was measured by the modified Borg scale. Bodyplethysmography and health-related quality of life (HRQoL) questionnaires were used. Patients suffering from deventilation syndrome (defined as dyspnea of at least three points on the Borg scale after mask removal) were treated with non-invasive pursed lip breathing ventilation (PLBV) during the second night of the study. Results Eleven of 31 patients included (35%) met the given criteria for a deventilation syndrome. They reported significantly more dyspnea on the Borg scale directly after mask removal (mean: 7.2 ± 1.0) compared to measurement after 2 h (4.8 ± 2.6; p = 0.003). Initially, mean inspiratory vital capacity was significantly reduced (VCmax: 46 ± 16%) compared to 2 h later (54 ± 15%; p = 0.002), while no changes in pulse oximetry or blood gas analysis were observed. Patients who suffered from a deventilation syndrome had a significantly higher mean airway resistance (Reff: 320 ± 88.5%) than the patients in the control group (253 ± 147%; p = 0.021). They also scored significantly lower on the Severe Respiratory Insufficiency Questionnaire (SRI; mean: 37.6 ± 10.1 vs 50.6 ± 16.7, p = 0.027). After one night of ventilation in PLBV mode, mean morning dyspnea decreased significantly to 5.6 ± 2.0 compared to 7.2 ± 1.0 after established treatment (p = 0.019) and mean inspiratory vital capacity increased from 44 ± 16.0% to 48 ± 16.3 (p = 0.040). Conclusions The deventilation syndrome is a serious side effect of NIV in COPD patients, characterized by increase of dyspnea. It is associated with decrease in vital capacity, exercise tolerance after mask removal and lower HRQoL. Patients with high airway resistance are at greater risk of suffering from morning dyspnea. Ventilation in PLBV mode may prevent or improve the deventilation syndrome. Trial registration: The study was registered in the German Clinical Trials Register (DRKS00016941) on 09 April 2019.

Background: Non-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 Question: For patients presenting with acute hypercapnic respiratory failure, is HFNC an effective alternative to NIV in reducing the need for intubation?Methods: We 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.Results: We 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).Interpretation: The 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. [ABSTRACT FROM AUTHOR]

Abstract Background Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common presentation in emergency departments (ED) that can be fatal. This study aimed to develop a mortality risk assessment model for patients presenting to the ED with AECOPD and hypercapnic respiratory failure. Methods We analysed 601 participants who were presented to an ED of a tertiary hospital with AECOPD between 2018 and 2020. Patient demographics, vital signs, and altered mental status were assessed on admission; moreover, the initial laboratory findings and major comorbidities were assessed. We used least absolute shrinkage and selection operator (LASSO) regression to identify predictors for establishing a nomogram for in-hospital mortality. Predictive ability was assessed using the area under the receiver operating curve (AUC). A 500 bootstrap method was applied for internal validation; moreover, the model’s clinical utility was evaluated using decision curve analysis (DCA). Additionally, the nomogram was compared with other prognostic models, including CRB65, CURB65, BAP65, and NEWS. Results Among the 601 patients, 19 (3.16%) died during hospitalization. LASSO regression analysis identified 7 variables, including respiratory rate, PCO2, lactic acid, blood urea nitrogen, haemoglobin, platelet distribution width, and platelet count. These 7 variables and the variable of concomitant pneumonia were used to establish a predictive model. The nomogram showed good calibration and discrimination for mortality (AUC 0.940; 95% CI 0.895–0.985), which was higher than that of previous models. The DCA showed that our nomogram had clinical utility. Conclusions Our nomogram, which is based on clinical variables that can be easily obtained at presentation, showed favourable predictive accuracy for mortality in patients with AECOPD with hypercapnic respiratory failure.

Purpose: Our study investigates the correlation between thiol/disulfide homeostasis and mortality among chronic obstructive pulmonary disease (COPD) patients with hypercapnic respiratory failure (HRF). Materials and Methods: This cross-sectional prospective study comprises a total of 104 subjects, including 64 HRF patients admitted to the Emergency service due to respiratory failure and 40 healthy controls. HRF patients were further divided into two subgroups as those in whom mortality occured after 1 month (n=14), and those who survied (n=50). Thiol/disulfide homeostasis was evaluated using a novel and automated assay developed by Erel and Neselioglu. Results: The total thiol (TT) and native thiol (NT) levels were significantly lower in the HRF group than the control group, whereas the mean disulfide (Ds)/TT and Ds/NT values were significantly higher. The Ds levels were not significantly different between the groups. On the other hand, Ds, Ds/TT, and Ds/NT values of surviving HRF patients were significantly lower than those of the HRF patients who died. In this article we found that Ds may be an indicator of mortality in COPD (sensitivity: 85.7%, specificity: 70%, AUC: 0.793, 95% CI: 0.673-0.884, p

Background: Non-invasive ventilation (NIV) is a recommended treatment for COPD patients suffering from chronic hypercapnic respiratory failure. Prolonged dyspnea after mask removal in the morning, often referred to as deventilation syndrome, is a common side effect but has been poorly characterized yet. This study aimed to explore the pathomechanism, identify risk factors and possible treatment strategies for the deventilation syndrome. Methods: A prospective, controlled, non-blinded study was conducted. After a night with established NIV therapy, the patients underwent spirometry, blood gas analyses and 6-min walking tests (6MWT) directly, at 2 and 4 h after mask removal. Dyspnea was measured by the modified Borg scale. Bodyplethysmography and health-related quality of life (HRQoL) questionnaires were used. Patients suffering from deventilation syndrome (defined as dyspnea of at least three points on the Borg scale after mask removal) were treated with non-invasive pursed lip breathing ventilation (PLBV) during the second night of the study. Results: Eleven of 31 patients included (35%) met the given criteria for a deventilation syndrome. They reported significantly more dyspnea on the Borg scale directly after mask removal (mean: 7.2 ± 1.0) compared to measurement after 2 h (4.8 ± 2.6; p = 0.003). Initially, mean inspiratory vital capacity was significantly reduced (VCmax: 46 ± 16%) compared to 2 h later (54 ± 15%; p = 0.002), while no changes in pulse oximetry or blood gas analysis were observed. Patients who suffered from a deventilation syndrome had a significantly higher mean airway resistance (Reff: 320 ± 88.5%) than the patients in the control group (253 ± 147%; p = 0.021). They also scored significantly lower on the Severe Respiratory Insufficiency Questionnaire (SRI; mean: 37.6 ± 10.1 vs 50.6 ± 16.7, p = 0.027). After one night of ventilation in PLBV mode, mean morning dyspnea decreased significantly to 5.6 ± 2.0 compared to 7.2 ± 1.0 after established treatment (p = 0.019) and mean inspiratory vital capacity increased from 44 ± 16.0% to 48 ± 16.3 (p = 0.040). Conclusions: The deventilation syndrome is a serious side effect of NIV in COPD patients, characterized by increase of dyspnea. It is associated with decrease in vital capacity, exercise tolerance after mask removal and lower HRQoL. Patients with high airway resistance are at greater risk of suffering from morning dyspnea. Ventilation in PLBV mode may prevent or improve the deventilation syndrome. Trial registration: The study was registered in the German Clinical Trials Register (DRKS00016941) on 09 April 2019. [ABSTRACT FROM AUTHOR]

Thyroid cancer is a type of malignancy that is considered to have a low morbidity and an indolent disease course in most patients. Though some of its pathologic variants such as anaplastic carcinoma may present with advanced disease staging, it is important to consider the possibility of metastasis to thyroid which may present like a thyroid primary. Solid organ carcinomas form the bulk of the uncommon metastasis to the thyroid, though sarcomas from various organs also rarely exhibit this activity. Literature demonstrating sound diagnostic criteria for these occurrences is sparse. We present a case of uterine sarcoma with distant metastasis to the thyroid gland that initially presented as hypercapnic respiratory failure. Only an inpatient episode of uterine bleeding prompted our team to explore the potential of a metastatic process. Our diagnosis was made utilizing a multidisciplinary approach that we feel is important for clinicians dealing with metastatic disease to the thyroid. In addition to sound physical exam, and use of appropriate imaging modality, we feel it is essential to utilize a detailed cytohistologic specimen evaluation, immunohistochemistry, and genetic sequencing to effectively work up such patients. Although our patient did not survive her hospital stay, we hope this paper brings greater awareness of this malignancy and acts as a benchmark for diagnosing such an unusual remote primary. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory failure (ARF) is one of the most common causes of intensive care unit (ICU) admission and in-hospital mortality. In South Korea, about 25% of patients admitted to the ICU require mechanical ventilation. The in-hospital mortality rate of these patients is 48%. Respiratory failure can be categorized based on pathophysiologic derangements, and the treatment options vary depending on their classification. This study discusses the status and treatment strategies of patients with ARF in Korea. Current Concepts: The most common treatment for ARF was conventional oxygen therapy, being used at least once in 7.0% of all admitted adult patients and 85.1% of patients admitted with respiratory failure. High-flow oxygen therapy was required in 1.4% of all admissions and 17.2% of respiratory failure-related admissions. High-flow oxygen therapy was attempted in 19.1% of patients who needed invasive mechanical ventilation. Non-invasive positive pressure ventilation (NIV) was used in 0.4% of all admissions and 5.1% of respiratory failure-related admissions. Hypercapnic respiratory failure (57.1%) was the most common reason for NIV use. Invasive mechanical ventilation was required in 2.8% of all admissions and 33.8% of respiratory failure-related admissions. Discussion and Conclusion: Despite its clinical significance, no large-scale studies have been performed on the etiology, treatment, and prognosis of patients with ARF in South Korea. A multicenter or a Korean National Health Insurance Service database study is necessary to accurately identify the characteristics, diagnose problems, and develop treatment guidelines for patients with ARF in South Korea. [ABSTRACT FROM AUTHOR]

Abstract Chronic obstructive pulmonary disease (COPD) is expected to be the 3rd leading cause of death worldwide by 2020. Despite improvements in survival by using acute non-invasive ventilation (NIV) to treat patients with exacerbations of COPD complicated by acute hypercapnic respiratory failure (AHRF), these patients are at high risk of readmission and further life-threatening events, including death. Recent studies suggested that NIV at home can reduce readmissions, but in a small proportion of patients, and with a high level of expertise. Other studies, however, do not show any benefit of home NIV. This could be related to the fact that respiratory failure in patients with stable COPD and their response to mechanical ventilation are influenced by several pathophysiological factors which frequently coexist in the same patient to varying degrees. These pathophysiological factors might influence the success of home NIV in stable COPD, thus long-term NIV specifically adapted to a patient’s “phenotype” is likely to improve prognosis, reduce readmission to hospital, and prevent death. In view of this conundrum, Rescue2-monitor (R2M), an open-label, prospective randomized, controlled study performed in patients with hypercapnic COPD post-AHRF, will investigate the impact of the quality of nocturnal NIV on the readmission-free survival. The primary objective is to show that any of 3 home NIV strategies (“rescue,” “non-targeted,” and “targeted”) will improve readmission-free survival in comparison to no-home NIV. The “targeted” group of patients will receive a treatment with personalized (targeted) ventilation settings and extensive monitoring. Furthermore, the influence of comorbidities typical for COPD patients, such as cardiac insufficiency, OSA, or associated asthma, on ventilation outcomes will be taken into consideration and reasons for non-inclusion of patients will be recorded in order to evaluate the percentage of ventilated COPD patients that are screening failures. ClinicalTrials.gov NCT03890224 . Registered on March 26, 2019.

Abstract Background Invasive mechanical ventilation is lifesaving in the setting of severe acute respiratory failure but can cause ventilation-induced lung injury. Advances in extracorporeal CO2 removal (ECCO2R) technologies may facilitate more protective lung ventilation in acute respiratory distress syndrome, and enable earlier weaning and/or avoid invasive mechanical ventilation entirely in chronic obstructive pulmonary disease exacerbations. We evaluated the in vitro CO2 removal capacity of the novel PrismaLung+ ECCO2R device compared with two existing gas exchangers. Methods The in vitro CO2 removal capacity of the PrismaLung+ (surface area 0.8 m2, Baxter) was compared with the PrismaLung (surface area 0.35 m2, Baxter) and A.L.ONE (surface area 1.35 m2, Eurosets) devices, using a closed-loop bovine blood–perfused extracorporeal circuit. The efficacy of each device was measured at varying pCO2 inlet (pinCO2) levels (45, 60, and 80 mmHg) and blood flow rates (Q B) of 200–450 mL/min; the PrismaLung+ and A.L.ONE devices were also tested at a Q B of 600 mL/min. The amount of CO2 removed by each device was assessed by measurement of the CO2 infused to maintain circuit equilibrium (CO2 infusion method) and compared with measured CO2 concentrations in the inlet and outlet of the CO2 removal device (blood gas analysis method). Results The PrismaLung+ device performed similarly to the A.L.ONE device, with both devices demonstrating CO2 removal rates ~ 50% greater than the PrismaLung device. CO2 removal rates were 73 ± 4.0, 44 ± 2.5, and 72 ± 1.9 mL/min, for PrismaLung+, PrismaLung, and A.L.ONE, respectively, at Q B 300 mL/min and pinCO2 45 mmHg. A Bland–Altman plot demonstrated that the CO2 infusion method was comparable to the blood gas analysis method for calculating CO2 removal. The resistance to blood flow across the test device, as measured by pressure drop, varied as a function of blood flow rate, and was greatest for PrismaLung and lowest for the A.L.ONE device. Conclusions The newly developed PrismaLung+ performed more effectively than PrismaLung, with performance of CO2 removal comparable to A.L.ONE at the flow rates tested, despite the smaller membrane surface area of PrismaLung+ versus A.L.ONE. Clinical testing of PrismaLung+ is warranted to further characterize its performance.

Background: Acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a common presentation in emergency departments (ED) that can be fatal. This study aimed to develop a mortality risk assessment model for patients presenting to the ED with AECOPD and hypercapnic respiratory failure.Methods: We analysed 601 participants who were presented to an ED of a tertiary hospital with AECOPD between 2018 and 2020. Patient demographics, vital signs, and altered mental status were assessed on admission; moreover, the initial laboratory findings and major comorbidities were assessed. We used least absolute shrinkage and selection operator (LASSO) regression to identify predictors for establishing a nomogram for in-hospital mortality. Predictive ability was assessed using the area under the receiver operating curve (AUC). A 500 bootstrap method was applied for internal validation; moreover, the model's clinical utility was evaluated using decision curve analysis (DCA). Additionally, the nomogram was compared with other prognostic models, including CRB65, CURB65, BAP65, and NEWS.Results: Among the 601 patients, 19 (3.16%) died during hospitalization. LASSO regression analysis identified 7 variables, including respiratory rate, PCO2, lactic acid, blood urea nitrogen, haemoglobin, platelet distribution width, and platelet count. These 7 variables and the variable of concomitant pneumonia were used to establish a predictive model. The nomogram showed good calibration and discrimination for mortality (AUC 0.940; 95% CI 0.895-0.985), which was higher than that of previous models. The DCA showed that our nomogram had clinical utility.Conclusions: Our nomogram, which is based on clinical variables that can be easily obtained at presentation, showed favourable predictive accuracy for mortality in patients with AECOPD with hypercapnic respiratory failure. [ABSTRACT FROM AUTHOR]

Background/aim: Treatment of severe hypercapnic respiratory failure (HRF) has some challenges in patients with chronic obstructive pulmonary disease (COPD) and acute respiratory distress syndrome (ARDS), especially when lung protective ventilation (LPV) strategies are required. Extracorporeal CO2 removal (ECCO2R) therapy is an emerging option to manage hypercapnia while allowing LPV in these cases. However, further data on ECCO2R use is still needed to make clear recommendations. Materials and methods: This study was conducted on patients admitted to intensive care unit (ICU) between January 1st, 2016 to December 31st, 2019. The medical records were retrospectively scanned in institutional software database. Patients who received invasive mechanic ventilation (iMV) support due to severe HRF related to COPD or ARDS were included in the analyses. Patients were grouped according to treatment approaches as that ECCO2R therapy in addition to conventional treatments and conventional treatments alone (controls). Groups were compared for 28-day survival, iMV duration, and length of stay (LOS). Results: ECCO2R therapy was noted in 75 of the cases among included 395 patients (COPD n = 256, ARDS n = 139) out of scanned 1715 medical records. The survival rate of ECCO2R patients was 68% and significantly higher than 58% survival rate of controls (p = 0.025), with relative risk reduction (RRR) = 0.16, absolute risk reduction (ARR)= 0.10, number need to treat (NNT) = 10, and odds ratio (OR) = 1.5. In addition, iMV duration (12.8 ± 2.6 vs. 17.1 ± 4.9 days, p = 0.007) and LOS (16.9 ± 4.1 vs. 18.9 ± 5.5 days, p = 0.032) were significantly shorter than controls. Repeated measure analyses showed that LPV settings were successfully provided by 72 h of ECCO2R therapy. Subgroup analyses according to diagnoses of COPD and ARDS also favored ECCO2R. Conclusion: ECCO2R therapy significantly improved survival, iMV duration and LOS in patients with severe HRF due to COPD or ARDS, and successfully provided LPV approaches. Further studies are needed to assess promising benefits of ECCO2R therapy. [ABSTRACT FROM AUTHOR]

Objective: To investigate the epidemiology, clinical features, treatment and outcome of Noninvasive ventilation (NIV)‐treated acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients in secondary hospitals of Shanghai. Method: Relying on Shanghai alliances for respiratory diseases, a retrospective observational study was performed in 34 secondary hospitals of Shanghai. The AECOPD patients treated with NIV and admitted to the respiratory department or respiratory intensive care unit were recruited between December 1, 2016, and November 30, 2017. Results: There were 555 patients finally recruited in this study. The age was 75.8 ± 9.6 years old and 380 patients (68.5%) were male. 70.5% of all patients had respiratory acidosis (pH <7.35). 55.3% of all patients received nebulised bronchodilator and 77.7% were treated with systemic or inhaled corticosteroids during hospitalisation. 525 patients (94.6%) recovered successfully and the mortality was 3.2%. The hospitalisation was 15.3 ± 6.7 days and hospital expenses were 22 911 ± 13 595 RMB. Inadequate and nonstandard drug treatments were the most important problems during management. Conclusion: The NIV can be successfully used for AECOP patients in local hospitals of Shanghai, but accompanied by high costs and long hospital stays. However, the treatments for exacerbation and stable COPD patients are still insufficient. [ABSTRACT FROM AUTHOR]

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Type 2 respiratory failure, or hypercapnic respiratory failure, is brought on by low oxygenation (hypoxemia) and inadequate breathing (hypercapnia). It is produced by factors that can create an imbalance between the requirement and capacity of the respiratory system. The factors can include an increased requirement for muscles of respiration, reduction in their strength or effectiveness, or impediment of the ventilatory drive. Rarely, it can be caused by the bare lymphocyte syndrome (BLS), which usually affects young children and has a poor prognosis with accompanying debilitating disabilities. This is a case report that shares the unique findings of a 13-year-old patient with type 1 BLS and atopy, who is suffering from type 2 respiratory failure. She is susceptible to respiratory tract infections and has been treated for bronchopneumonia and tuberculosis in the past. She has been on assisted ventilation for the past 3.5 months, along with supplementary nutrition. She has been evaluated meticulously and methodically, ruling out other causes of her respiratory failure. Recognizing the root cause aided in her therapy and preventing mortality. This has been determined using clinical findings, lab results, and radiological reports. The diagnosis of hypercapnic respiratory failure was confirmed via an arterial blood gas analysis, whereas that of BLS was confirmed through a whole genome sequence test. Management entailed addressing the underlying cause, optimizing ventilation, and using mechanical ventilation to maintain respiratory function. Early detection and timely intervention were critical in enhancing the outcome for the patient., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bhatnagar et al.)

An emerging body of literature describes the prevalence and consequences of hypercapnic respiratory failure. While device qualifications, documentation practices, and previously performed clinical studies often encourage conceptualizing patients as having a single "cause" of hypercapnia, many patients encountered in practice have several contributing conditions. Physiologic and epidemiologic data suggest that sleep-disordered breathing-particularly obstructive sleep apnea (OSA)-often contributes to the development of hypercapnia. In this review, the authors summarize the frequency of contributing conditions to hypercapnic respiratory failure among patients identified in critical care, emergency, and inpatient settings with an aim toward understanding the contribution of OSA to the development of hypercapnia., Competing Interests: Disclosure B.W. Locke. receives research funding from the American Thoracic Society ASPIRE Fellowship and the National Institutes of Health under the Ruth L. Kirschstein National Research Service Award 5T32HL105321 J.P. Brown. no conflicts of interest. K.M. Sundar is co-founder of Hypnoscure LLC—a software application for population management of sleep apnea through the University of Utah Technology Commercialization Office., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We present two cases of acute hypercapnic respiratory failure due to diaphragmatic dysfunction secondary to bilateral phrenic nerve paralysis, in patients who were receiving immunotherapy for melanoma. Bilateral diaphragmatic paralysis is an uncommon cause of acute or sub-acute hypercapnic respiratory failure which causes severe breathlessness, orthopnoea and potentially death. Immune checkpoint inhibitors are now standard of care in several solid organ malignancies. However, their use is associated with a risk of developing autoimmune toxicities, which includes mononeuritis. Our two cases demonstrate the potential difficulties in recognising acute hypercapnic respiratory failure and diagnosis of the rare disorder of bilateral diaphragmatic dysfunction, with consequent delays in appropriate management. The occurrence of this rare condition in association with checkpoint inhibitor immunotherapy suggests a possible autoimmune mechanism. Awareness that this rare cause of respiratory failure may occur in patients receiving checkpoint inhibitor therapy might facilitate earlier diagnosis and treatment.

Abstract Myxedema coma is an emergency presentation of hypothyroidism, and cardiopulmonary manifestations of the disease are related to a high mortality rate. We herein report a case of myxedema coma accompanied by sick sinus syndrome requiring temporary cardiac pacing and hypercapnic respiratory failure in an 87‐year‐old woman. This case is unique because both of the cardiac and pulmonary manifestations were reversible and successfully treated with thyroid hormone replacement. Our case indicates that early detection of the condition and administration of levothyroxine are essential to improve the life‐threatening condition and avoid invasive treatment such as permanent pacemaker implantation or intubation.

Background: Invasive mechanical ventilation is lifesaving in the setting of severe acute respiratory failure but can cause ventilation-induced lung injury. Advances in extracorporeal CO2 removal (ECCO2R) technologies may facilitate more protective lung ventilation in acute respiratory distress syndrome, and enable earlier weaning and/or avoid invasive mechanical ventilation entirely in chronic obstructive pulmonary disease exacerbations. We evaluated the in vitro CO2 removal capacity of the novel PrismaLung+ ECCO2R device compared with two existing gas exchangers. Methods: The in vitro CO2 removal capacity of the PrismaLung+ (surface area 0.8 m2, Baxter) was compared with the PrismaLung (surface area 0.35 m2, Baxter) and A.L.ONE (surface area 1.35 m2, Eurosets) devices, using a closed-loop bovine blood–perfused extracorporeal circuit. The efficacy of each device was measured at varying pCO2 inlet (pinCO2) levels (45, 60, and 80 mmHg) and blood flow rates (QB) of 200–450 mL/min; the PrismaLung+ and A.L.ONE devices were also tested at a QB of 600 mL/min. The amount of CO2 removed by each device was assessed by measurement of the CO2 infused to maintain circuit equilibrium (CO2 infusion method) and compared with measured CO2 concentrations in the inlet and outlet of the CO2 removal device (blood gas analysis method). Results: The PrismaLung+ device performed similarly to the A.L.ONE device, with both devices demonstrating CO2 removal rates ~ 50% greater than the PrismaLung device. CO2 removal rates were 73 ± 4.0, 44 ± 2.5, and 72 ± 1.9 mL/min, for PrismaLung+, PrismaLung, and A.L.ONE, respectively, at QB 300 mL/min and pinCO2 45 mmHg. A Bland–Altman plot demonstrated that the CO2 infusion method was comparable to the blood gas analysis method for calculating CO2 removal. The resistance to blood flow across the test device, as measured by pressure drop, varied as a function of blood flow rate, and was greatest for PrismaLung and lowest for the A.L.ONE device. Conclusions: The newly developed PrismaLung+ performed more effectively than PrismaLung, with performance of CO2 removal comparable to A.L.ONE at the flow rates tested, despite the smaller membrane surface area of PrismaLung+ versus A.L.ONE. Clinical testing of PrismaLung+ is warranted to further characterize its performance. [ABSTRACT FROM AUTHOR]

Extracorporeal CO2 removal is a highly promising support therapy for patients with hypercapnic respiratory failure but whose clinical implementation and patient benefit is hampered by high cost and highly specialized expertise required for safe use. Current approaches target removal of the gaseous CO2 dissolved in blood which limits their ease of clinical use as high blood flow rates are required to achieve physiologically significant CO2 clearance. Here, a novel hybrid approach in which a zero-bicarbonate dialysis is used to target removal of bicarbonate ion coupled to a gas exchange device to clear dissolved CO2, achieves highly efficiently total CO2 capture while maintaining systemic acid–base balance. In a porcine model of acute hypercapnic respiratory failure, a CO2-reduction of 61.4 ± 14.4 mL/min was achieved at a blood flow rate of 248 mL/min using pediatric-scale priming volumes. The dialyzer accounted for 81% of total CO2 capture with an efficiency of 33% with a minimal pH change across the entire circuit. This study demonstrates the feasibility of a novel hybrid CO2 capture approach capable of achieving physiologically significant CO2 removal at ultralow blood flow rates with low priming volumes while leveraging widely available dialysis platforms to enable clinical adoption. [ABSTRACT FROM AUTHOR]