Is there still a place for ECCO2R?

The therapeutic target of extracorporeal carbon dioxide removal (ECCO2R) is the elimination of carbon dioxide (CO2) from the blood across a gas exchange membrane without influencing oxygenation to a clinically relevant extent. In acute respiratory distress syndrome (ARDS), ECCO2R has been used to reduce tidal volume, plateau pressure, and driving pressure ("ultraprotective ventilation"). Despite achieving these goals, no benefits in outcome could be shown. Thus, in ARDS, the use of ECCO2R to achieve ultraprotective ventilation can no longer be recommended. Furthermore, ECCO2R has also been used to avoid intubation or facilitate weaning in obstructive lung failure as well as to avoid mechanical ventilation in patients during bridging to lung transplantation. Although these goals can be achieved in many patients, the effects on outcome still remain unclear due to lack of evidence. Despite involving less blood flow, smaller cannulas, and smaller gas exchange membranes compared with extracorporeal membrane oxygenation, ECCO2R bears a comparable risk of complications, especially bleeding. Trials to define indications and analyze the risk-benefit balance are needed prior to implementation of ECCO2R as a standard therapy. Consequently, until then, ECCO2R should be used in clinical studies and experienced centers only. This article is freely available.

A Comparison of the Outcomes of COVID-19 Vaccinated and Nonvaccinated Patients Admitted to an Intensive Care Unit in a Low-Middle-Income Country.

Patients critically afflicted with coronavirus disease 2019 (COVID-19) often need intensive care unit (ICU) admission, despite comprehensive vaccination campaigns. The challenges faced by healthcare systems in low-middle-income countries, including limited infrastructure and resources, play a pivotal role in shaping the outcomes for these patients. This study aimed to meticulously compare outcomes between COVID-19 vaccinated and nonvaccinated patients admitted to the ICU. In addition, demographic factors and the ICU course influencing mortality were also assessed. A retrospective review of records from the COVID-ICU of Aga Khan University Hospital spanning July 2021-March 2022 included 133 patients. Statistical analyses, encompassing the Mann-Whitney U-test and chi-square/Fisher exact test, discerned quantitative and qualitative differences. Stepwise multivariable logistic regression models with forward selection identified factors associated with hospital mortality. Results revealed comparable cohorts: vaccinated (48.13%) and nonvaccinated (51.87%). Vaccinated individuals, characterized by advanced age and higher Charlson Comorbidity Index, exhibited more critical disease (89.1%; p value: 0.06), acute respiratory distress syndrome (96.9%; p value: 0.013) and elevated inflammatory markers. Despite these differences, both cohorts exhibited similar overall outcomes. Factors such as decreased PaO2/FiO2 ratio on admission and complications during ICU stay were significantly associated with in-hospital mortality. In conclusion, despite advanced age and increased frailty among vaccinated patients, their mortality rate remained comparable to nonvaccinated counterparts. These findings underscore the pivotal role of vaccination in mitigating severe outcomes within this vulnerable population.

Respiratory insufficiency in an infant with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a rare presentation in the pediatric population. Whilst orthopedic manifestations are well-publicised, the multiple respiratory complications and mechanisms of respiratory failure in more severe cases are less well described. We report the clinical, radiological and histopathological details of the case of an infant with genetically-confirmed OI (Type 2) and associated respiratory insufficiency, as well as summarise the relevant existing literature. This case highlights the importance of the recognition of clinical challenges associated with the management of respiratory complications in a patient with OI.

Respiratory insufficiency after brain metastasectomy for extraskeletal Ewing sarcoma in an adult patient with mucopolysaccharidosis type II: a case report.

Mucopolysaccharidosis is a rare lysosomal storage disease caused by deficiencies in enzymes involved in the degradation of glycosaminoglycans. We report the case of an adult with mucopolysaccharidosis type II who developed respiratory insufficiency after brain metastasectomy for extraskeletal Ewing sarcoma. This report describes the case of a 35-year-old man with a mass on the left chest wall for 3 months. Magnetic resonance imaging and computed tomography revealed a large mass on the chest wall. Positron emission tomography revealed multiple metastatic lesions in the lungs, ribs, and sternum. A needle biopsy specimen confirmed extraskeletal Ewing sarcoma, and the fusion gene EWS-FLI1 was positive. Subsequently, multidrug chemotherapy was administered. During radiotherapy for the primary lesion, progressive convulsions occurred suddenly. Computed tomography of the brain revealed metastasis in the frontal lobe. Brain metastasectomy was scheduled; however, endotracheal intubation was not possible because of the deformity of the glottis, and emergency tracheostomy was performed. Thereafter, granulation tissue proliferated in reaction to the tracheostomy cannulae in the trachea, and respiratory insufficiency persisted. Because of the rapid growth of an intrathoracic recurrent tumor, the patient passed away 2 months after brain surgery. This is the first report of sarcoma in a patient with mucopolysaccharidosis. Respiratory management is difficult in patients with mucopolysaccharidosis, especially under general anesthesia. Orthopedic surgeons should be aware that surgical planning must be performed carefully when soft tissue sarcomas occur in patients with mucopolysaccharidosis.

Can ketamine administration prevent intubation in patients who cannot comply with NIV due to agitation?

BACKGROUND: In patients presenting to the emergency department (ED) with acute respiratory failure, non-invasive mechanical ventilation (NIMV) is applied when conventional oxygen support is not sufficient. Patients who are agitated often have very low NIMV compliance and a transition to invasive mechanical ventilation (IMV) is often required. To avoid IMV, a suitable sedative agent can be utilized. The aim of this research is to investigate the relationship between ketamine administration to patients who are non-compliant with NIMV due to agitation and the outcome of their intubation. METHODS: This retrospective study included patients with acute respiratory failure who were admitted to the ED from 2021 to 2022 and used Richmond Agitation Sedation Scale (RASS) to identify agitation level of patients. The relationship between ketamine administration in this patient group and NIMV compliance and intubation rate was evaluated. RESULTS: A total of 81 patients, including 35 (43.2%) men and 46 (56.8%) women, were included in the study. Of these patients, 46 (56.8%) were intubated despite ketamine administration, while 35 (43.2%) were compliant with NIMV and were not intubated. When evaluating the RASS, which shows the agitation levels of the patients, the non-intubated group was found to be 2.17 ± 0.68, while the intubated group was 2.66 ± 0.73, and it was statistically significant that the NIMV intubated group was higher (p = 0.003). CONCLUSION: This study showed that agitation can impair NIMV compliance in patients with acute respiratory failure. However, a significant proportion of this patient group can be avoided through IMV with proper sedative agents.

Use of an Integrated Pulmonary Index pathway decreased unplanned ICU admissions in elderly patients with rib fractures.

Unplanned intensive care unit (ICU) admission (UIA) is a Trauma Quality Improvement Program benchmark that is associated with increased morbidity, mortality, and length of stay (LOS). Elderly patients with multiple rib fractures are at increased risk of respiratory failure. The Integrated Pulmonary Index (IPI) assesses respiratory compromise by incorporating SpO2, respiratory rate, pulse, and end-tidal CO2 to yield an integer between 1 and 10 (worst and best). We hypothesized that IPI monitoring would decrease UIA for respiratory failure in elderly trauma patients with rib fractures. Methods: Elderly (≥65 years old) trauma inpatients admitted to a level 1 trauma center from February 2020 to February 2023 were retrospectively studied during the introduction of IPI monitoring on the trauma floor. Patients with ≥4 rib fractures (or ≥2 with history of chronic obstructive pulmonary disease) were eligible for IPI monitoring and were compared with a group of chest Abbreviated Injury Scale score of 3 (≥3 rib fractures) patients who received usual care. Nurses contacted the surgeon for IPI ≤7. Patient intervention was left to the discretion of the provider. The primary endpoint was UIA for respiratory failure. Secondary endpoints were overall UIA, mortality, and LOS. Statistical analysis was performed using χ2 test and Student's t-test, with p<0.05 considered significant. Results: A total of 110 patients received IPI monitoring and were compared with 207 patients who did not. The IPI cohort was comparable to the non-IPI cohort in terms of gender, Injury Severity Score, Abbreviated Injury Scale, mortality, and LOS. There were 16 UIAs in the non-IPI cohort and two in the IPI cohort (p=0.039). There were no UIAs for respiratory failure in the IPI group compared with nine in the non-IPI group (p=0.03). Conclusion: IPI monitoring is an easy-to-set up tool with minimal risk and was associated with a significant decrease in UIA in elderly patients with rib fracture. Level of evidence: Level III, therapeutic/care management.

Use of prototype bi-nasal prongs for noninvasive ventilation in foals.

BACKGROUND: Noninvasive ventilation (NIV) provides effective respiratory support in foals, but face masks are poorly tolerated and associated with hypercapnia. Bi-nasal prongs might be a more effective device interface in foals. OBJECTIVES: To compare bi-nasal prongs and masks for NIV in foals with pharmacologically induced respiratory insufficiency. ANIMALS: Six healthy foals. METHODS: In a randomized cross-over study, sedated foals received NIV delivered by mask or bi-nasal prongs, with the treatment repeated using the alternative device interface after a 3-day rest period. After periods of spontaneous ventilation through the allocated interface, with and without supplementary O2 (T2-T3), foals were subject to 10-minute treatment periods of NIV at different pressure support (5 or 10 cmH2O) and end-expiratory pressure settings (5 or 10 cmH2O), with and without supplementary O2 (T4-T7). Vital signs, arterial blood gases, spirometry, and gas exchange data were measured in the final 2 minutes of each treatment window. RESULTS: Bi-nasal prongs were well tolerated and required less manual positioning or monitoring compared to the mask. Partial pressure of carbon dioxide did not increase during NIV with bi-nasal prongs and was lower than observed with masks (mean difference, 8.2 mmHg [95% confidence interval, 4.1-12.2 mmHg] at T6). Oxygenation and respiratory mechanics were improved in all foals and not different between device interfaces. CONCLUSIONS AND CLINICAL IMPORTANCE: Nasal prongs were well tolerated, had similar effects on respiratory function, and appeared to ameliorate hypercapnia observed previously during NIV in foals.

The pleural gradient does not reflect the superimposed pressure in patients with class III obesity.

BACKGROUND: The superimposed pressure is the primary determinant of the pleural pressure gradient. Obesity is associated with elevated end-expiratory esophageal pressure, regardless of lung disease severity, and the superimposed pressure might not be the only determinant of the pleural pressure gradient. The study aims to measure partitioned respiratory mechanics and superimposed pressure in a cohort of patients admitted to the ICU with and without class III obesity (BMI ≥ 40 kg/m2), and to quantify the amount of thoracic adipose tissue and muscle through advanced imaging techniques. METHODS: This is a single-center observational study including ICU-admitted patients with acute respiratory failure who underwent a chest computed tomography scan within three days before/after esophageal manometry. The superimposed pressure was calculated from lung density and height of the largest axial lung slice. Automated deep-learning pipelines segmented lung parenchyma and quantified thoracic adipose tissue and skeletal muscle. RESULTS: N = 18 participants (50% female, age 60 [30-66] years), with 9 having BMI < 30 and 9  ≥ 40 kg/m2. Groups showed no significant differences in age, sex, clinical severity scores, or mortality. Patients with BMI ≥ 40 exhibited higher esophageal pressure (15.8 ± 2.6 vs. 8.3 ± 4.9 cmH2O, p = 0.001), higher pleural pressure gradient (11.1 ± 4.5 vs. 6.3 ± 4.9 cmH2O, p = 0.04), while superimposed pressure did not differ (6.8 ± 1.1 vs. 6.5 ± 1.5 cmH2O, p = 0.59). Subcutaneous and intrathoracic adipose tissue were significantly higher in subjects with BMI ≥ 40 and correlated positively with esophageal pressure and pleural pressure gradient (p < 0.05). Muscle areas did not differ between groups. CONCLUSIONS: In patients with class III obesity, the superimposed pressure does not approximate the pleural pressure gradient, which is higher than in patients with lower BMI. The quantity and distribution of subcutaneous and intrathoracic adiposity also contribute to increased pleural pressure gradients in individuals with BMI ≥ 40. This study introduces a novel physiological concept that provides a solid rationale for tailoring mechanical ventilation in patients with high BMI, where specific guidelines recommendations are lacking.

Understanding ventilator-induced lung injury: The role of mechanical power.

Mechanical ventilation stands as a life-saving intervention in the management of respiratory failure. However, it carries the risk of ventilator-induced lung injury. Despite the adoption of lung-protective ventilation strategies, including lower tidal volumes and pressure limitations, mortality rates remain high, leaving room for innovative approaches. The concept of mechanical power has emerged as a comprehensive metric encompassing key ventilator parameters associated with the genesis of ventilator-induced lung injury, including volume, pressure, flow, resistance, and respiratory rate. While numerous animal and human studies have linked mechanical power and ventilator-induced lung injury, its practical implementation at the bedside is hindered by calculation challenges, lack of equation consensus, and the absence of an optimal threshold. To overcome the constraints of measuring static respiratory parameters, dynamic mechanical power is proposed for all patients, regardless of their ventilation mode. However, establishing a causal relationship is crucial for its potential implementation, and requires further research. The objective of this review is to explore the role of mechanical power in ventilator-induced lung injury, its association with patient outcomes, and the challenges and potential benefits of implementing a ventilation strategy based on mechanical power.

Lower or Higher Oxygenation Targets in ICU patients with COVID-19 - A secondary Bayesian analysis of the HOT-COVID trial.

BACKGROUND: In the Handling Oxygenation Targets in COVID-19 (HOT-COVID) trial, a partial pressure of arterial oxygen (PaO2) target of 60 mmHg compared to 90 mmHg resulted in more days alive without life support at 90 days in adult ICU patients with coronavirus disease 2019 (COVID-19) and hypoxemia. The trial was stopped after enrolling 726 of 780 planned patients due to slow recruitment. Here, we present the preplanned Bayesian analysis of the HOT-COVID trial. RESEARCH QUESTION: What are the probabilities of any and of clinically relevant benefits from a PaO2 target of 60 mmHg versus 90 mmHg in adult ICU patients with COVID-19 and hypoxemia, and is there heterogeneity of treatment effects (HTE) according to selected baseline characteristics? STUDY DESIGN: and Methods We analyzed days alive without life support and 90-day mortality in the HOT-COVID intention-to-treat population (n=697) using Bayesian general linear models to assess probabilities for benefit or harm, including clinically relevant benefits defined as >1 day alive without life support and >2 percentage points lower 90-day mortality. HTE was evaluated based on baseline SOFA scores, PaO2:FiO2, norepinephrine doses, and lactate concentrations. RESULTS: The mean difference in days alive without life support was 5.7 days (95% credible interval (CrI): 0.2 to 11.2), with a 95.2% probability of clinically relevant benefit and a 98.0% probability of any benefit from the lower PaO2 target. The risk difference in 90-day mortality was -4.6 percentage points (95% CrI: -11.8 to 2.6), with a 76.5% probability of a clinically relevant benefit from the lower target. HTE analyses revealed potential interaction with baseline norepinephrine dose and lactate concentrations for both outcomes. INTERPRETATION: In ICU patients with COVID-19 and hypoxemia, we found high probability for a clinically relevant benefit of targeting a PaO2 of 60 mmHg vs. 90 mmHg on number of days alive without life support.

ECMO in severe hypoxemia post liver transplant for hepatopulmonary syndrome.

Hepatopulmonary syndrome (HPS) poses a significant challenge in liver transplant patients, affecting between 10% and 30% of candidates. Historically, HPS was considered a contraindication for liver transplantation due to its association with high mortality rates. However, recent studies have shown improvements in pulmonary function post-transplant, leading to the inclusion of these patients as candidates. Despite this progress, approximately one-fifth of liver transplant recipients develop severe postoperative hypoxia, further complicating their clinical course and contributing to increased mortality. The management of post-transplant HPS involves various strategies, including extracorporeal membrane oxygenation (ECMO), although its use remains infrequently reported. Theoretical models suggest that oxygenation typically improves within 10 days post-transplant, while resolution of HPS may take 6-12 months, making ECMO an attractive possibility as a bridge to recovery in this population. We present a case were ECMO was used in this context.

Adaptive Pressure Control-Continuous Mandatory Ventilation Versus Volume Control-Continuous Mandatory Ventilation: Factors Associated With Initiation, Maintenance, and Adjustment.

BACKGROUND: Adaptive pressure control-continuous mandatory ventilation (APC-CMV) is a frequently utilized ventilator mode in ICU settings. This analysis compared APC-CMV and traditional volume control-continuous mandatory ventilation (VC-CMV) mode, describing factors associated with initiation, maintenance, and changes in settings of each mode. METHODS: We analyzed ventilator data from a retrospective electronic health record data set collected as part of a quality improvement project in a single academic ICU. The majority ventilator mode was defined as the mode comprising the highest proportion of mechanical ventilation time. Multivariable logistic regression was used to identify variables associated with initial and majority APC-CMV or VC-CMV modes. Wilcoxon rank-sum tests were used to compare ventilator setting changes/d and sedation as a function of APC-CMV and VC-CMV majority modes. RESULTS: Among 1,213 subjects initiated on mechanical ventilation from January 2013-March 2017, 68% and 24% were initiated on APC-CMV and VC-CMV, respectively, which composed 62% and 21% of the majority ventilator modes. Age, sex, race, and ethnicity were not associated with the initial or majority APC-CMV or VC-CMV modes. Subjects initiated on APC-CMV spent 88% of the mechanical ventilation time on APC-CMV mode. Compared to VC-CMV, subjects with APC-CMV majority mode experienced more ventilator setting changes/d (1.1 vs 0.8, P < .001). There were no significant differences in sedative medications when comparing subjects receiving APC-CMV versus VC-CMV majority modes. CONCLUSIONS: APC-CMV was highly utilized in the medical ICU. Subjects on APC-CMV had more ventilator setting changes/d than those on VC-CMV. APC-CMV offered no advantage of reduced setting adjustments or less sedation compared to VC-CMV.

Respiratory Compromise Related to Primary Histoplasmosis Infection in Two Pediatric Patients.

Primary infection related to the fungus, histoplasmosis, is generally asymptomatic in immunocompetent hosts. Calcified granulomas may be noted incidentally on radiologic imaging such as chest radiographs or computed tomography imaging. However, even in immunocompetent hosts, these primary infections occasionally result in end-organ involvement including respiratory compromise. Histoplasmosis should be included in the differential diagnosis of patients presenting with respiratory involvement and mediastinal adenopathy. We present two pediatric-aged patients who developed pulmonary involvement related to a primary histoplasmosis infection that resulted in mediastinal and tracheal lymphadenopathy. These led to respiratory compromise due to pleural effusion in the first patient and tracheal compression in the second. In this paper, the basic microbiology of Histoplasma capsulatum is presented, previous reports of primary respiratory involvement presented, and diagnostic and therapeutic options discussed.

The Role of Cognition, Affective Symptoms, and Apathy in Treatment Adherence with Noninvasive Home Mechanical Ventilation in Myotonic Dystrophy.

Background: Chronic respiratory failure often occurs in myotonic dystrophy type 1 (DM1) and can be treated with noninvasive home mechanical ventilation (HMV). Treatment adherence with HMV is often suboptimal in patients with DM1, but the reasons for that are not well understood. Objective: The aim of this exploratory study was to gain insight in the prevalence of mild cognitive impairment, affective symptoms, and apathy and to investigate their role in HMV treatment adherence in DM1. Methods: The Montreal Cognitive Assessment (MoCA), the Hospital Anxiety and Depression Scale (HADS), and the Apathy Evaluation Scale (AES) were used to assess cognition, affective symptoms, and apathy in DM1 patients that use HMV. Patients with low treatment adherence (average daily use HMV <5 h or <80% of the days) were compared with patients with high treatment adherence (average daily use of HMV≥5 h and ≥80% of the days). Results: Sixty patients were included. Abnormal scores were found in 40% of the total group for the MoCA, in 72-77% for the AES, and in 18% for HADS depression. There was no difference between the high treatment adherence group (n = 39) and the low treatment adherence group (n = 21) for the MoCA, AES, and HADS depression. The HADS anxiety was abnormal in 30% of the total group, and was significantly higher in the low treatment adherence group (p = 0.012). Logistic regression analysis revealed that a higher age and a higher BMI were associated with a greater chance of high treatment adherence. Conclusions: This exploratory study showed that cognitive impairment and apathy are frequently present in DM1 patients that use HMV, but they are not associated with treatment adherence. Feelings of anxiety were associated with low treatment adherence. Higher age and higher BMI were associated with high treatment adherence with HMV.

EFFICACY OF NON-INVASIVE VENTILATION WITH EXPIRATORY WASHOUT IN STABLE COPD PATIENTS: A RANDOMIZED CROSS-OVER PILOT.

Background: A non-invasive ventilation (NIV) mask has been designed to deliver NIV with expiratory washout (EW) to improve efficacy of ventilation by optimizing clearance of expired gases from the anatomic dead-space. This study compared the performance and comfort of a novel investigational mask with EW with a conventional mask during NIV therapy.Methods: In this pilot cross-over study, participants with severe stable chronic obstructive pulmonary disease (COPD) attended a single visit to receive bi-level NIV through two masks; the investigational mask with EW, and a conventional mask. The order of mask use was randomly allocated, and each mask was used for 60-minutes with a 30-to-60-minute washout in between. The primary outcome was transcutaneous carbon dioxide (PtCO2) at 60 minutes. Other physiologic and NIV device variables were also assessed.Results: The mean difference [95% CI] in the PtCO2 between the investigational and conventional masks at 60 minutes, adjusted for baseline, was -0.74 mmHg [-2.81 to 1.33, P=0.45]. The investigational mask with EW elicited a lower tidal volume (-128.7 mL [-190.0 to -67.3], P<0.001) and minute ventilation (-2.28 L·min-1 [-3.12 to -1.43], P<0.001), and a higher leak (7.96 L·min-1 [4.39 to 11.54], P<0.001), than the conventional mask. There were no significant differences in other physiological responses or ratings of dyspnoea or comfort.Conclusions: NIV therapy delivered using a novel mask with EW was similarly effective at reducing PtCO2, while the delivered tidal volume and minute ventilation were significantly lower, when compared to a conventional mask in participants with severe COPD.

High PEEP/low FiO2 ventilation is associated with lower mortality in COVID-19.

RATIONALE: The positive end-expiratory pressure (PEEP) strategy in patients with coronavirus 2019 (COVID-19) acute respiratory distress syndrome (ARDS) remains debated. Most studies originate from the initial waves of the pandemic. Here we aimed to assess the impact of high PEEP/low FiO2 ventilation on outcomes during the second wave in the Netherlands. METHODS: Retrospective observational study of invasively ventilated COVID-19 patients during the second wave. Patients were categorized based on whether they received high PEEP or low PEEP ventilation according to the ARDS Network tables. The primary outcome was ICU mortality, and secondary outcomes included hospital and 90-day mortality, duration of ventilation and length of stay, and the occurrence of kidney injury. Propensity matching was performed to correct for factors with a known relationship to ICU mortality. RESULTS: This analysis included 790 COVID-ARDS patients. At ICU discharge, 32 (22.5%) out of 142 high PEEP patients and 254 (39.2%) out of 848 low PEEP patients had died (HR 0.66 [0.46-0.96]; P = 0.03). High PEEP was linked to improved secondary outcomes. Matched analysis did not change findings. CONCLUSIONS: High PEEP ventilation was associated with improved ICU survival in patients with COVID-ARDS.

Healthcare Use and Costs in Children Receiving Home Mechanical Ventilation in Ontario: A 14-Year Cohort Study.

Rationale: Home mechanical ventilation (HMV) is an advanced medical therapy offered to children with medical complexity. Despite the growing pediatric HMV population in North America, there are limited studies describing healthcare use and predictors of highest costs using robust health administrative data. Objectives: To describe patterns of healthcare use and costs in children receiving HMV over a 14-year period in Ontario, Canada. Methods: We conducted a retrospective population-based cohort study (April 1, 2003, to March 31, 2017) of children aged 0-18 years receiving HMV via invasive mechanical ventilation or noninvasive ventilation. Paired t tests compared healthcare system use and costs 2 years before and 2 years after HMV approval. We developed linear models to analyze variables associated with children in the top quartile of health service use and costs. Results: We identified 835 children receiving HMV. In the 2 years after HMV approval compared with the 2 years prior, children had decreased hospitalization days (median, 9 [interquartile range, 3-30] vs. 29 [6-99]; P < 0.0001) and intensive care unit admission days (6.6 [1.9-18.0] vs. 17.1 [3.3-70.9]; P < 0.0001) but had increased homecare service approvals (195 [24-522] vs. 40 [12-225]; P < 0.0001) and outpatient pulmonology visits (3 [1-4] vs. 2 [1-3]; P < 0.0001). Total healthcare costs were higher in the 2 years after HMV approval (mean, CAD$164,892 [standard deviation, CAD$214,187] vs. CAD$128,941 [CAD$194,199]; P < 0.0001). However, all-cause hospital admission costs were reduced (CAD$66,546 [CAD$142,401] vs. CAD$81,578 [CAD$164,672]; P < 0.0001). The highest total 2-year costs were associated with invasive mechanical ventilation (odds ratio [OR], 3.45; 95% confidence interval [CI], 2.24-5.31; reference noninvasive ventilation), number of medical devices at home (OR, 1.63; 95% CI, 1.35-1.96; reference no technology), and increased healthcare costs in the year before HMV initiation (OR, 2.23; 95% CI, 1.84-2.69). Conclusions: Children progressing to the need for HMV represent a worsening in their respiratory status that will undoubtedly increase healthcare use and costs. We found that the initiation of HMV in these children can reduce inpatient healthcare use and costs but can still increase overall healthcare expenditures, especially in the outpatient setting.

Lower or higher oxygenation targets in the intensive care unit: an individual patient data meta-analysis.

PURPOSE: Optimal oxygenation targets for patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are not clearly defined due to substantial variability in design of previous trials. This study aimed to perform a pre-specified individual patient data meta-analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) and the Handling Oxygenation Targets in coronavirus disease 2019 (COVID-19) (HOT-COVID) trials to compare targeting a partial pressure of arterial oxygen (PaO2) of 8-12 kPa in adult ICU patients, assessing both benefits and harms. METHODS: We assessed 90-day all-cause mortality and days alive without life support in 90 days using a generalised mixed model. Heterogeneity of treatment effects (HTE) was evaluated in 14 subgroups, and results graded using the Instrument to assess the Credibility of Effect Modification Analyses (ICEMAN). RESULTS: At 90 days, mortality was 40.4% (724/1792) in the 8 kPa group and 40.9% (733/1793) in the 12 kPa group (risk ratio, 0.99; 95% confidence interval [CI] 0.92-1.07; P = 0.80). No difference was observed in number of days alive without life support. Subgroup analyses indicated more days alive without life support in COVID-19 patients targeting 8 kPa (P = 0.04) (moderate credibility), and lower mortality (P = 0.03) and more days alive without life support (P = 0.02) in cancer-patients targeting 12 kPa (low credibility). CONCLUSION: This study reported no overall differences comparing a PaO2 target of 8-12 kPa on mortality or days alive without life support in 90 days. Subgroup analyses suggested HTE in patients with COVID-19 (moderate credibility) and cancer (low credibility).

Time-Dependent Changes in Pulmonary Turnover of Thrombocytes During Critical COVID-19.

OBJECTIVES BACKGROUND: Under normal conditions, pulmonary megakaryocytes are an important source of circulating thrombocytes, causing thrombocyte counts to be higher in arterial than venous blood. In critical COVID-19, thrombocytes may be removed from the circulation by the lungs because of immunothrombosis, possibly causing venous thrombocyte counts to be higher than arterial thrombocyte counts. In the present study, we investigated time-dependent changes in pulmonary turnover of thrombocytes during critical COVID-19 by measuring arteriovenous thrombocyte differences. We hypothesized that the early stages of the disease would be characterized by a net pulmonary removal of circulating thrombocytes because of immunothrombosis and that later stages would be characterized by a net pulmonary release of thrombocytes as normal pulmonary function is restored. DESIGN: Cohort study with repeated measurements of arterial and central venous thrombocyte counts. SETTING: ICU in a large university hospital. PATIENTS: Thirty-one patients with critical COVID-19 that were admitted to the ICU and received invasive or noninvasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We found a significant positive association between the arteriovenous thrombocyte difference and time since symptom debut. This finding indicates a negative arteriovenous thrombocyte difference and hence pulmonary removal of thrombocytes in the early stages of the disease and a positive arteriovenous thrombocyte difference and hence pulmonary release of thrombocytes in later stages. Most individual arteriovenous thrombocyte differences were smaller than the variance coefficient of the analysis. CONCLUSIONS: The results of this study support our hypothesis that early stages of critical COVID-19 are characterized by pulmonary removal of circulating thrombocytes because of immunothrombosis and that later stages are characterized by the return of normal pulmonary release of thrombocytes. However, in most cases, the arteriovenous thrombocyte difference was too small to say anything about pulmonary thrombocyte removal and release on an individual level.

Extracorporeal Membrane Oxygenation for Respiratory Failure: A Narrative Review.

Extracorporeal membrane oxygenation support for respiratory failure in the intensive care unit continues to have an expanded role in select patients. While acute respiratory distress syndrome remains the most common indication, extracorporeal membrane oxygenation may be used in other causes of refractory hypoxemia and/or hypercapnia. The most common configuration is veno-venous extracorporeal membrane oxygenation; however, in specific cases of refractory hypoxemia or right ventricular failure, some patients may benefit from veno-pulmonary extracorporeal membrane oxygenation or veno-venoarterial extracorporeal membrane oxygenation. Patient selection and extracorporeal circuit management are essential to successful outcomes. This narrative review explores the physiology of extracorporeal membrane oxygenation, indications and contraindications, ventilator management, extracorporeal circuit management, troubleshooting hypoxemia, complications, and extracorporeal membrane oxygenation weaning in patients with respiratory failure. As the footprint of extracorporeal membrane oxygenation continues to expand, it is essential that clinicians understand the underlying physiology and management of these complex patients.