Risk factors for COVID-19 associated pulmonary aspergillosis and outcomes in patients with acute respiratory failure in a respiratory sub-intensive care unit.

BACKGROUND: COVID-19-associated pulmonary aspergillosis (CAPA) is burdened by high mortality. Data are lacking about non-ICU patients. Aims of this study were to: (i) assess the incidence and prevalence of CAPA in a respiratory sub-intensive care unit, (ii) evaluate its risk factors and (iii) impact on in-hospital mortality. Secondary aims were to: (i) assess factors associated to mortality, and (ii) evaluate significant features in hematological patients. MATERIALS AND METHODS: This was a single-center, retrospective study of COVID-19 patients with acute respiratory failure. A cohort of CAPA patients was compared to a non-CAPA cohort. Among patients with CAPA, a cohort of hematological patients was further compared to another of non-hematological patients. RESULTS: Three hundred fifty patients were included in the study. Median P/F ratio at the admission to sub-intensive unit was 225 mmHg (IQR 155-314). 55 (15.7%) developed CAPA (incidence of 5.5%). Eighteen had probable CAPA (37.3%), 37 (67.3%) possible CAPA and none proven CAPA. Diagnosis of CAPA occurred at a median of 17 days (IQR 12-31) from SARS-CoV-2 infection. Independent risk factors for CAPA were hematological malignancy [OR 1.74 (95%CI 0.75-4.37), p = 0.0003], lymphocytopenia [OR 2.29 (95%CI 1.12-4.86), p = 0.02], and COPD [OR 2.74 (95%CI 1.19-5.08), p = 0.014]. Mortality rate was higher in CAPA cohort (61.8% vs 22.7%, p < 0.0001). CAPA resulted an independent risk factor for in-hospital mortality [OR 2.92 (95%CI 1.47-5.89), p = 0.0024]. Among CAPA patients, age > 65 years resulted a predictor of mortality [OR 5.09 (95% CI 1.20-26.92), p = 0.035]. No differences were observed in hematological cohort. CONCLUSION: CAPA is a life-threatening condition with high mortality rates. It should be promptly suspected, especially in case of hematological malignancy, COPD and lymphocytopenia.

Pre- and intra-operative risk factors predict postoperative respiratory failure after minimally invasive oesophagectomy.

OBJECTIVES: Severe pulmonary complications such as postoperative respiratory failure can occur after minimally invasive oesophagectomy. However, the risk factors have not been well identified. The goal of this study was to develop a predictive model for the occurrence of postoperative respiratory failure with a large sample. METHODS: We collected data from patients with oesophageal cancer who had a minimally invasive oesophagectomy at Shanghai Chest Hospital from 2019 to 2022. Univariable and backward stepwise logistic regression analysis of 19 pre- and intra-operative factors was used before model fitting, and its performance was evaluated with the receiver operating characteristic curve. Internal validation was assessed with a calibration plot, decision curve analysis and area under the curve with 95% confidence intervals, obtained from 1000 resamples set by the bootstrap method. RESULTS: This study enrolled 2,386 patients, 57 (2.4%) of whom developed postoperative respiratory failure. Backward stepwise logistic regression analysis revealed that age, body mass index, cardiovascular disease, diabetes, diffusion capacity of the lungs for carbon monoxide, tumour location and duration of chest surgery ≥101.5 min were predictive factors. A predictive model was constructed and showed acceptable performance (area under the curve: 0.755). The internal validation with the bootstrap method proves the good agreement for prediction and reality. CONCLUSIONS: Obesity, severe diffusion dysfunction and upper segment oesophageal cancer were strong predictive factors. The established predictive model has acceptable predictive validity for postoperative respiratory failure after minimally invasive oesophagectomy, which may improve the identification of high-risk patients and enable health-care professionals to perform risk assessment for postoperative respiratory failure at the initial consultation.

Outcomes of Acute Respiratory Failure in Patients With Cancer in the United States.

OBJECTIVE: To determine the epidemiological effect-magnitude and outcomes of patients with cancer vs those without cancer who are hospitalized with acute respiratory failure (ARF). PATIENTS AND METHODS: We reviewed hospitalizations within the National Inpatient Sample (NIS) database between January 1, 2016, and December 31, 2018. Patients were classified based on a diagnosis of solid-organ cancer, hematologic cancer, or no cancer. Noninvasive positive pressure ventilation (NIPPV) failure was defined as patients who initially received NIPPV and had progression to invasive mechanical ventilation. Weighted samples were used to derive population estimates. RESULTS: During the study period, there were an estimated 8,837,209 admissions with ARF in the United States, 8.9% (783,625) of which had solid-organ cancer and 2.0% (176,095) had hematologic cancers. Annually, 319,907 patients with cancer are admitted with ARF, with 27.3% (87,302) requiring invasive mechanical ventilation and 10.0% (31,998) requiring NIPPV. In-hospital mortality was higher in patients with cancer vs those without cancer (24.0% [76,813] vs 12.3% [322,465]; P<.001), and this proprotion persisted when stratified by the highest method of oxygen delivery. Patients with cancer had longer hospital length of stay (7.0 days [3.0 to 12.0 days] vs 5.0 days [3.0 to 10.0 days]; P<.001) and were more likely to have NIPPV failure (14.9% [3,992] vs 12.8% [41,875]). Compared with those with solid-organ cancer, patients with hematologic cancers experienced worse outcomes. The association between underlying cancer diagnosis and outcomes remained consistent when adjusted for age, sex, and comorbidities. CONCLUSION: In the United States, patients with cancer account for over 10% of ARF hospital admissions (959,720 of 8,837,209). They experience an approximately 2-fold higher mortality versus those without cancer. Those with hematologic cancers appear to experience worse outcomes than patients with solid-organ cancers.

Prognostic factors and outcomes of invasive pulmonary aspergillosis, a retrospective hospital-based study.

Objective: Invasive pulmonary aspergillosis (IPA) affects immunocompromised hosts and is associated with higher risks of respiratory failure and mortality. However, the clinical outcomes of different IPA types have not been identified. Methods: Between September 2002 and May 2021, we retrospectively enrolled patients with IPA in Taichung Veterans General Hospital, Taiwan. Cases were classified as possible IPA, probable IPA, proven IPA, and putative IPA according to EORTC/MSGERC criteria and the AspICU algorithm. Risk factors of respiratory failure, kidney failure, and mortality were analyzed by logistic regression. A total of 3-year survival was assessed by the Kaplan-Meier method with log-rank test for post-hoc comparisons. Results: We included 125 IPA patients (50: possible IPA, 47: probable IPA, 11: proven IPA, and 17: putative IPA). Comorbidities of liver cirrhosis and solid organ malignancy were risk factors for respiratory failure; diabetes mellitus and post-liver or kidney transplantation were related to kidney failure. Higher galactomannan (GM) test optical density index (ODI) in either serum or bronchoalveolar lavage fluid was associated with dismal outcomes. Probable IPA and putative IPA had lower 3-year respiratory failure-free survival compared to possible IPA. Probable IPA and putative IPA exhibited lower 3-year renal failure-free survival in comparison to possible IPA and proven IPA. Putative IPA had the lowest 3-year overall survival rates among the four IPA groups. Conclusion: Patients with putative IPA had higher mortality rates than the possible, probable, or proven IPA groups. Therefore, a prompt diagnosis and timely treatment are warranted for patients with putative IPA.

Global, Regional and National Trends in the Burden of Neonatal Respiratory Failure and essentials of its diagnosis and management from 1992 to 2022: a scoping review.

Neonatal respiratory failure (NRF) is an emergency which has not been examined extensively. We critically synthesized the contemporary in-hospital prevalence, mortality rate, predictors, aetiologies, diagnosis and management of NRF to better formulate measures to curb its burden. We searched MEDLINE and Google Scholar from 01/01/1992 to 31/12/2022 for relevant publications. We identified 237 papers from 58 high-income and low-and middle-income countries (LMICs). NRF prevalence ranged from 0.64 to 88.4% with some heterogeneity. The prevalence was highest in Africa, the Middle East and Asia. Globally as well as in Asia and the Americas, respiratory distress syndrome (RDS) was the leading aetiology of NRF. Neonatal sepsis was first aetiology in Africa, whereas in both Europe and the Middle East it was transient tachypnoea of the newborn. Independent predictors of NRF were prematurity, male gender, ethnicity, low/high birth weight, young/advanced maternal age, primiparity/multiparity, maternal smoking, pregestational/gestational diabetes mellitus, infectious anamneses, antepartum haemorrhage, gestational hypertensive disorders, multiple pregnancy, caesarean delivery, antenatal drugs, foetal distress, APGAR score, meconium-stained amniotic fluid and poor pregnancy follow-up. The NRF-related in-hospital mortality rate was 0.21-57.3%, highest in Africa, Asia and the Middle East. This death toll was primarily due to RDS globally and in all regions. Clinical evaluation using the Silverman-Anderson score was widely used and reliable. Initial resuscitation followed by specific management was the common clinical practice. CONCLUSION: NRF has a high burden globally, driven by RDS, especially in LIMCs where more aggressive treatment and innovations, preferably subsidized, are warranted to curb its alarming burden. WHAT IS KNOWN: • Neonatal respiratory failure is a frequent emergency associated with a significant morbidity and mortality, yet there is no comprehensive research paper summarizing its global burden. • Neonatal respiratory failure needs prompt diagnosis and treatment geared at improving neonatal survival. WHAT IS NEW: • Neonatal respiratory failure has an alarmingly high global burden largely attributed to Respiratory distress syndrome. Low resource settings are disproportionately affected by the burden of neonatal respiratory failure. • Independent preditors of neonatal respiratory failure are several but can be classified into foetal, maternal and obstetrical factors. An illustrative pedagogical algorithm is provided to facilitate diagnosis and management of neonatal respiratory failure by healthcare providers.

Predicting the risk of acute respiratory failure among asthma patients-the A2-BEST2 risk score: a retrospective study.

Objectives: Acute respiratory failure (ARF) is a common complication of bronchial asthma (BA). ARF onset increases the risk of patient death. This study aims to develop a predictive model for ARF in BA patients during hospitalization. Methods: This was a retrospective cohort study carried out at two large tertiary hospitals. Three models were developed using three different ways: (1) the statistics-driven model, (2) the clinical knowledge-driven model, and (3) the decision tree model. The simplest and most efficient model was obtained by comparing their predictive power, stability, and practicability. Results: This study included 398 patients, with 298 constituting the modeling group and 100 constituting the validation group. Models A, B, and C yielded seven, seven, and eleven predictors, respectively. Finally, we chose the clinical knowledge-driven model, whose C-statistics and Brier scores were 0.862 (0.820-0.904) and 0.1320, respectively. The Hosmer-Lemeshow test revealed that this model had good calibration. The clinical knowledge-driven model demonstrated satisfactory C-statistics during external and internal validation, with values of 0.890 (0.815-0.965) and 0.854 (0.820-0.900), respectively. A risk score for ARF incidence was created: The A2-BEST2 Risk Score (A2 (area of pulmonary infection, albumin), BMI, Economic condition, Smoking, and T2(hormone initiation Time and long-term regular medication Treatment)). ARF incidence increased gradually from 1.37% (The A2-BEST2 Risk Score ≤ 4) to 90.32% (A2-BEST2 Risk Score ≥ 11.5). Conclusion: We constructed a predictive model of seven predictors to predict ARF in BA patients. This predictor's model is simple, practical, and supported by existing clinical knowledge.

Respiratory syncytial virus burden and risk factors for severe disease in patients presenting to the emergency department with flu-like symptoms or acute respiratory failure.

BACKGROUND: Predictors of Respiratory Syncytial Virus (RSV) infection and determinants of RSV unfavorable outcomes are still unclear. We assessed RSV burden and investigated the risk factors associated with RSV positive swab and RSV severe disease. METHODS: A retrospective, single center, cohort study included all consecutive patients referred to the emergency department of L. Sacco University Hospital (Milan) with flu-like symptoms or acute respiratory failure (aRF) tested per protocol for SARS-CoV-2, RSV, Influenza A (InvA) during the 2022-2023 autumn/winter season. Clinical characteristics and patients' outcomes were registered. Respiratory failure, need for respiratory support, shock, sepsis or in-hospital death defined severe disease. MAIN FINDINGS: The analysis included 717 patients (65.1% negative swab, 14.1% InvA, 8.5% RSV, 8.6% SARS-CoV-2, 3.6% other viruses). Compared with the study cohort, RSV patients had the highest occurrence of aRF (62.7%) and severe disease (70.5%); mortality was similar to InvA (6.6% vs 5.9%, p = 0.874). Compared with InvA patients, RSV patients were older (p = 0.009), had higher Charlson index (p = 0.001), higher prevalence of chronic heart failure (p = 0.001) and were more frequently on ICS (p = 0.026) and immunosuppressants (p = 0.018). Heart failure [OR (95%CI):3.286 (1.031-10.835); p = 0.041], chronic exposure to ICS [OR (95%CI):2.377 (1.254-4.505); p = 0.008] and immunosuppressants [OR (95%CI):3.661 (1.246-10.754); p = 0.018] predicted RSV infection. Glycaemia ≥120 mg/dL [OR (95%CI):5.839 (1.155-29.519); p = 0.033], leucocytes ≥8000 cells/µL [OR (95%CI):5.929 (1.090-32.268); p = 0.039], and past/active smoking [OR (95%CI):7.347 (1.301-41.500); p = 0.024] predicted severe RSV disease. CONCLUSIONS: RSV infection is associated with significant mortality and morbidity. Preventive strategies for RSV infection such as vaccination are highly warranted, especially in older patients with cardiovascular and chronic respiratory conditions.

Risk Factors for Severe Respiratory Syncytial Virus Infection in Hospitalized Children.

BACKGROUND: RSV often leads to hospitalization, and accurate knowledge of risk factors is crucial. METHODS: We retrospectively analyzed laboratory-confirmed RSV hospitalizations regarding pregnancy factors, birth status, cigarette smoke exposure, nutrition, social conditions, clinical presentation, and severe disease defined as a need for passive oxygen therapy (pO2Tx), the presence of pneumonia, respiratory failure, intensive care unit (ICU) transfer, and prolonged hospitalization. RESULTS: A univariate analysis included 594 children (median age 4 months) and revealed a pO2Tx relationship with age ≤ 3 months (OR = 1.56), prematurity (OR = 1.71), being born during RSV season (OR = 1.72), smoke exposure during pregnancy (both parents (OR = 2.41, father (OR = 1.8)), dyspnea (OR = 5.09), and presence of apnea (OR = 5.81). Pneumonia was associated with maternal smoke exposure (OR = 5.01), fever (OR = 3.92), dyspnea (OR = 1.62), history of aspiration (OR = 4.63), and inversely with age ≤ 3 months (OR = 0.45). Respiratory failure was associated with prematurity (OR = 3.13) and apnea (OR = 18.78), while the lower odds were associated with older age (OR = 0.57 per month) and presence of fever (OR = 0.11). ICU transfer was associated with apnea (OR = 17.18), but an inverse association was observed with age (OR = 0.54) and fever (OR = 0.11). A prolonged hospital stay was associated with prematurity (OR = 1.76), low birth weight (OR = 2.89), aspiration (OR = 4.93), and presence of fever (OR = 1.51). CONCLUSIONS: Age (up to 3 months), prematurity, and presence of apnea are risk factors for a severe RSV course.

Obstructive sleep apnea is associated with use of assisted ventilation among children with bronchopulmonary dysplasia hospitalized with respiratory illness: A nationwide inpatient cohort.

OBJECTIVE (S): Children with bronchopulmonary dysplasia (BPD) are at higher risk of respiratory insufficiency during respiratory illness. We aimed to investigate whether obstructive sleep apnea (OSA) is associated with increased morbidity among children with BPD hospitalized with acute respiratory illnesses. STUDY DESIGN: Hospital discharge records were obtained from the Kid's Inpatient Database for children <21 years of age with BPD hospitalized for acute respiratory illness between 1997 and 2012. Acute respiratory illnesses included bacterial and/or viral pneumonia, bronchiolitis, acute upper respiratory tract infections, aspiration pneumonia, or asthma exacerbation. The primary exposure was OSA. The primary outcome was invasive mechanical ventilation (IMV), and secondary outcomes were noninvasive mechanical ventilation (NIMV), length of hospital stay (LOS), and inflation-adjusted cost of hospitalization (IACH). Multivariable regression was conducted to ascertain the associations between OSA and primary and secondary outcomes accounting for BPD-associated comorbidities. RESULTS: Among 33,640 hospitalizations of children with BPD for acute respiratory illness, there were 607 (1.8%) cases with comorbid OSA vs. 33,033 (98.2%) controls without OSA. Patients with OSA were more likely to have aspiration pneumonia, central sleep apnea, obesity, laryngeal stenosis, congenital airway, and skull/face/jaw anomalies. Multivariable regression showed that OSA was associated with IMV (OR 1.45, 95% CI 1.09-1.94, p = 0.012) and NIMV (OR 2.61, 95% CI 1.71-3.98, p < 0.001), but not LOS or IACH. CONCLUSIONS: In BPD patients hospitalized with acute respiratory illness, having OSA is associated with increased risks for respiratory insufficiency requiring noninvasive or invasive mechanical ventilation. Clinicians should consider OSA, along with other BPD-associated comorbidities, in the management of this population.

Pulmonary comorbidities in psoriasis are associated with a high risk of respiratory failure.

OBJECTIVES: To identify respiratory comorbidities associated with a high risk of developing respiratory failure in subjects with psoriasis. METHODS: This was a cross-sectional analysis of data from subjects enrolled in the UK Biobank cohort. All diagnoses were self-reported. The risk of each respiratory comorbidity was compared by logistic regression models adjusting for age, sex, weight, diabetes mellitus, and smoking history; the risk of comorbid respiratory failure for each pulmonary comorbidity was also compared. RESULTS: Of the 472,782 Caucasian subjects in the database, 3,285 self-reported a diagnosis of psoriasis. More men and smokers reported psoriasis and were older, had higher weight and body mass index, and lower pulmonary function than non-psoriatic subjects. Those with psoriasis were at significantly higher risk for multiple pulmonary comorbidities compared to those without psoriasis. Furthermore, those with psoriasis had a higher risk for respiratory failure accompanied by asthma and airflow limitation than non-psoriatic subjects. CONCLUSIONS: Subjects with psoriasis and pulmonary comorbidities, such as asthma and airflow limitation, are at increased risk for respiratory failure. Common immunopathological links implicating a 'skin-lung axis' may underlie psoriasis and pulmonary comorbidities.

Etiologies and Outcome of Patients with Solid Tumors Admitted to ICU with Acute Respiratory Failure: A Secondary Analysis of the EFRAIM Study.

BACKGROUND: Acute respiratory failure (ARF) remains the most frequent reason for ICU admission in patients who are immunocompromised. This study reports etiologies and outcomes of ARF in subjects with solid tumors. METHODS: This study was a post hoc analysis of the EFRAIM study, a prospective multinational cohort study that included 1611 subjects who were immunocompromised and with ARF admitted to the ICU. Subjects with solid tumors admitted to the ICU with ARF were included in the analysis. RESULTS: Among the subjects from the EFRAIM cohort, 529 subjects with solid tumors (32.8%) were included in the analysis. At ICU admission, the median (interquartile range) Sequential Organ Failure Assessment score was 5 (3-9). The types of solid tumor were mostly lung cancer (n = 111, 21%), breast cancer (n = 52, 9.8%), and digestive cancer (n = 47, 8.9%). A majority, 379 subjects (71.6%) were full code at ICU admission. The ARF was caused by bacterial or viral infection (n = 220, 41.6%), extrapulmonary sepsis (n = 62, 11.7%), or related to cancer or treatment toxicity (n = 83, 15.7%), or fungal infection (n = 23, 4.3%). For 63 subjects (11.9%), the ARF etiology remained unknown after an extensive diagnostic workup. The hospital mortality rate was 45.7% (n = 232/508). Hospital mortality was independently associated with chronic cardiac failure (odds ratio 1.78, 95% CI 1.09-2.92; P = .02), lung cancer (odds ratio 2.50, 95% CI 1.51-4.19; P < .001), day 1 Sequential Organ Failure Assessment score (odds ratio 1.97, 95% CI 1.32-2.96; P < .001). ARF etiologies other than infectious, related to cancer, or treatment toxicity were associated with better outcomes (odds ratio 0.32, 95% CI 0.16-0.61; P < .001). CONCLUSIONS: Infectious diseases remained the most frequent cause of ARF in subjects with solid tumors admitted to the ICU. Hospital mortality was related to severity at ICU admission, previous comorbidities, and ARF etiologies related to non-malignant causes or pulmonary embolism. Lung tumor was also independently associated with higher mortality.

Efficacy of prophylactic high-flow nasal cannula therapy for postoperative pulmonary complications after pediatric cardiac surgery: a prospective single-arm study.

PURPOSE: This study investigated the incidence of postoperative pulmonary complications (PPC) when high-flow nasal cannula therapy (HFNC) is used prophylactically after pediatric cardiac surgery, and evaluated its efficacy. METHODS: This was a single-arm prospective interventional study that was conducted in a tertiary teaching hospital with eight beds in the pediatric cardiac ICU after approval by the Ethics Committee. One-hundred children under the age of 48 months who were scheduled for cardiac surgery for congenital heart disease were recruited. HFNC was used for 24 h after extubation at a 2 L/kg/min flow rate. The primary outcome was the incidence of PPC within 48 h after extubation. PPC was defined as atelectasis and acute respiratory failure meeting certain criteria. We considered prophylactic HFNC as effective if the prevalence of PPC was < 10%, based on previous reports of reintubation rates of 6%-9% after pediatric cardiac surgery. RESULTS: A total of 91 patients were finally included in the analysis. The incidence of PPC within 48 h after extubation was 18.7%, whereas atelectasis was observed in 13.2%, and acute respiratory failure in 8.8%. Reintubation rate within 48 h after extubation was 0%. CONCLUSIONS: We found the incidence of PPC with prophylactic HFNC after planned extubation after pediatric cardiac surgery. However, the incidence was > 10%; therefore, we could not demonstrate its efficacy in this single-arm study. Further studies are needed to investigate whether the HFNC could be adapted as first-line oxygen therapy after pediatric cardiac surgery.

Sarcopenia index as a predictor of clinical outcomes among older adult patients with acute exacerbation of chronic obstructive pulmonary disease: a cross-sectional study.

BACKGROUND: Sarcopenia is a geriatric syndrome with progressive loss of skeletal muscle mass and function and has a negative impact on clinical outcomes associated with chronic obstructive pulmonary disease (COPD). Recently, the sarcopenia index (SI) was developed as a surrogate marker of sarcopenia based upon the serum creatinine to cystatin C ratio. We aimed to assess the value of SI for predicting clinically important outcomes among elderly patients with acute exacerbation of COPD (AECOPD). METHODS: This cross-sectional study included elderly patients with AECOPD in China from 2017 to 2021. Clinical data were collected from medical records, and serum creatinine and cystatin C were measured. Outcomes included respiratory failure, heart failure, severe pneumonia, invasive mechanical ventilation, and mortality. Binary logistic regression was used to analyze the association between SI and clinical outcomes. RESULTS: A total of 306 patients (260 men, 46 women, age range 60-88 years) were enrolled in this study. Among the total patients, the incidence of respiratory failure and severe pneumonia was negatively associated with SI values. After adjusting for potential confounding factors, binary logistic regression analyses showed that a higher SI was still independently associated with a lower risk of respiratory failure (odds ratio [OR]: 0.27, 95% confidence interval [CI]: 0.13-0.56, P < 0.05). In subgroup analysis, the incidence of respiratory failure was negatively associated with SI values in groups with both frequent exacerbation and non-frequent exacerbation. After adjustment for potential confounders, binary logistic regression analyses showed that a higher SI was also independently associated with a lower risk of respiratory failure in both groups (OR: 0.19, 95% CI: 0.06-0.64 and OR: 0.31, 95% CI: 0.11-0.85). However, there were no significant differences in the correlations between SI and the risk of heart failure, invasive mechanical ventilation, and mortality in all groups. CONCLUSION: The SI based on serum creatinine and cystatin C can predict respiratory failure in patients with AECOPD and either frequent or infrequent exacerbations. This indicator provides a convenient tool for clinicians when managing patients with AECOPD in daily clinical practice.

The association of intraoperative low driving pressure ventilation and nonhome discharge: a historical cohort study.

PURPOSE: To evaluate whether intraoperative ventilation using lower driving pressure decreases the risk of nonhome discharge. METHODS: We conducted a historical cohort study of patients aged ≥ 60 yr who were living at home before undergoing elective, noncardiothoracic surgery at two tertiary healthcare networks in Massachusetts between 2007 and 2018. We assessed the association of the median driving pressure during intraoperative mechanical ventilation with nonhome discharge using multivariable logistic regression analysis, adjusted for patient and procedural factors. Contingent on the primary association, we assessed effect modification by patients' baseline risk and mediation by postoperative respiratory failure. RESULTS: Of 87,407 included patients, 12,584 (14.4%) experienced nonhome discharge. In adjusted analyses, a lower driving pressure was associated with a lower risk of nonhome discharge (adjusted odds ratio [aOR], 0.88; 95% confidence interval [CI], 0.83 to 0.93, per 10 cm H2O decrease; P < 0.001). This association was magnified in patients with a high baseline risk (aOR, 0.77; 95% CI, 0.73 to 0.81, per 10 cm H2O decrease, P-for-interaction < 0.001). The findings were confirmed in 19,518 patients matched for their baseline respiratory system compliance (aOR, 0.90; 95% CI, 0.81 to 1.00; P = 0.04 for low [< 15 cm H2O] vs high [≥ 15 cm H2O] driving pressures). A lower risk of respiratory failure mediated the association of a low driving pressure with nonhome discharge (20.8%; 95% CI, 15.0 to 56.8; P < 0.001). CONCLUSIONS: Intraoperative ventilation maintaining lower driving pressure was associated with a lower risk of nonhome discharge, which can be partially explained by lowered rates of postoperative respiratory failure. Future randomized controlled trials should target driving pressure as a potential intervention to decrease nonhome discharge.

RéSUMé: OBJECTIF: Évaluer si la ventilation peropératoire utilisant une pression motrice plus faible diminue le risque de congé hors domicile. MéTHODE: Nous avons réalisé une étude de cohorte historique de patients âgés de ≥ 60 ans vivant à la maison avant de bénéficier d'une chirurgie non cardiothoracique non urgente dans deux réseaux de soins de santé tertiaires du Massachusetts entre 2007 et 2018. Nous avons évalué l'association entre la pression motrice médiane pendant la ventilation mécanique peropératoire et le congé ailleurs qu'au domicile à l'aide d'une analyse de régression logistique multivariable, ajustée pour tenir compte des facteurs liés aux patients et à l'intervention. En fonction de l'association primaire, nous avons évalué la modification de l'effet par le risque initial des patients et la médiation par l'insuffisance respiratoire postopératoire. RéSULTATS: Sur les 87 407 patients inclus, 12 584 (14,4 %) ont reçu leur congé ailleurs qu'au domicile. Dans les analyses ajustées, une pression motrice plus faible était associée à un risque réduit de congé hors domicile (rapport de cotes ajusté [RCa], 0,88; intervalle de confiance [IC] à 95 %, 0,83 à 0,93, par diminution de 10 cm H2O; P < 0,001). Cette association a été amplifiée chez les patients présentant un risque initial élevé (RCa, 0,77; IC 95 %, 0,73 à 0,81, par diminution de 10 cm H2O, P-pour-interaction < 0,001). Les résultats ont été confirmés chez 19 518 patients appariés pour la compliance initiale de leur système respiratoire (RCa, 0,90; IC 95 %, 0,81 à 1,00; P = 0,04 pour des pressions motrices faibles [< 15 cm H2O] vs élevées [≥ 15 cm H2O]). Un risque plus faible d'insuffisance respiratoire a entraîné une association entre une faible pression motrice et un congé à l'extérieur du domicile (20,8 %; IC 95 %, 15,0 à 56,8 ; P < 0,001). CONCLUSION: La ventilation peropératoire maintenant une pression motrice plus faible a été associée à un risque plus faible de congé hors domicile, ce qui peut s'expliquer en partie par des taux réduits d'insuffisance respiratoire postopératoire. Les futures études randomisées contrôlées devraient cibler la pression motrice comme intervention potentielle pour réduire les congés hors domicile.

Impact of Prophylactic Corticosteroid Use on In-hospital Mortality and Respiratory Failure After Esophagectomy for Esophageal Cancer: Nationwide Inpatient Data Study in Japan.

OBJECTIVE: To assess the effect of preoperative prophylactic corticosteroid use on short-term outcomes after oncologic esophagectomy. BACKGROUND: Previous studies have shown that prophylactic corticosteroid use may decrease the risk of respiratory failure following esophagectomy by attenuating the perioperative systemic inflammation response. However, its effectiveness has been controversial, and its impact on mortality remains unknown. METHODS: Data of patients who underwent oncologic esophagectomy between July 2010 and March 2019 were extracted from a Japanese nationwide inpatient database. Stabilized inverse probability of treatment weighting, propensity score matching, and instrumental variable analyses were performed to investigate the associations between prophylactic corticosteroid use and short-term outcomes, such as in-hospital mortality and respiratory failure, adjusting for potential confounders. RESULTS: Among 35,501 eligible patients, prophylactic corticosteroids were used in 22,620 (63.7%) patients. In-hospital mortality, respiratory failure, and severe respiratory failure occurred in 924 (2.6%), 5440 (15.3%), and 2861 (8.1%) patients, respectively. In stabilized inverse probability of treatment weighting analyses, corticosteroids were significantly associated with decreased in-hospital mortality [odds ratio (OR)=0.80; 95% confidence interval (CI): 0.69-0.93], respiratory failure (OR=0.84; 95% CI: 0.79-0.90), and severe respiratory failure (OR=0.87; 95% CI: 0.80-0.95). Corticosteroids were also associated with decreased postoperative length of stay and total hospitalization costs. The proportion of anastomotic leakage did not differ with the use of Propensity score matching and instrumental variable analysis demonstrated similar results. CONCLUSIONS: Prophylactic corticosteroid use in oncologic esophagectomy was associated with lower in-hospital mortality as well as decreased respiratory failure and severe respiratory failure, suggesting a potential benefit for preoperative corticosteroid use in esophagectomy.

Association between choice of reversal agent for neuromuscular block and postoperative pulmonary complications in patients at increased risk undergoing non-emergency surgery: STIL-STRONGER, a multicentre matched cohort study.

BACKGROUND: Postoperative pulmonary complications are a source of morbidity after major surgery. In patients at increased risk of postoperative pulmonary complications we sought to assess the association between neuromuscular blocking agent reversal agent and development of postoperative pulmonary complications. METHODS: We conducted a retrospective matched cohort study, a secondary analysis of data collected in the prior STRONGER study. Data were obtained from the Multicenter Perioperative Outcomes Group. Included patients were aged 18 yr and older undergoing non-emergency surgery under general anaesthesia with tracheal intubation with neuromuscular block and reversal, who were predicted to be at elevated risk of postoperative pulmonary complications. This risk was defined as American Society of Anesthesiologists Physical Status 3 or 4 in patients undergoing either intrathoracic or intra-abdominal surgery who were either aged >80 yr or underwent a procedure lasting >2 h. Cohorts were defined by reversal with neostigmine or sugammadex. The primary composite outcome was the occurrence of pneumonia or respiratory failure. RESULTS: After matching by institution, sex, age (within 5 yr), body mass index, anatomic region of surgery, comorbidities, and neuromuscular blocking agent, 3817 matched pairs remained. The primary postoperative pulmonary complications outcome occurred in 224 neostigmine cases vs 100 sugammadex cases (5.9% vs 2.6%, odds ratio 0.41, P<0.01). After adjustment for unbalanced covariates, the adjusted odds ratio for the association between sugammadex use and the primary outcome was 0.39 (P<0.0001). CONCLUSIONS: In a cohort of patients at increased risk for pulmonary complications compared with neostigmine, use of sugammadex was independently associated with reduced risk of subsequent development of pneumonia or respiratory failure.

Opioid-Related Respiratory Depression in Non-Cancer Patients, as Reported in the Japanese Adverse Drug Event Report Database.

BACKGROUND: Opioid-induced respiratory depression (RD) is a potentially life-threatening adverse drug event. This study used the Japanese Adverse Drug Event Report (JADER) database to investigate the profile of opioid-related RD in non-cancer patients. METHODS: We analyzed data recorded in the JADER database between April 2004 and February 2020, which were downloaded from the Pharmaceutical and Medical Devices Agency website. Reporting odds ratios for RD were calculated for the 20 opioids approved in Japan, and daily dose and onset time were further analyzed for opioids used in chronic non-cancer pain (CNCP). RESULTS: Among the opioids, RD adverse event signals were detected for 22 combinations of opioids and administration routes in non-cancer patients. Of these combinations, transdermal buprenorphine and oral tramadol/acetaminophen were approved for CNCP and tended to be reported more frequently in elderly patients. The median daily doses of transdermal buprenorphine and oral tramadol/acetaminophen were 10.0 and 22.5 mg of daily oral morphine equivalent doses, respectively, which are within the standard range for starting dosage. The median time-to-onset of transdermal buprenorphine and oral tramadol/acetaminophen was 6.5 and 4.0 days, respectively, and 75% of cases were reported within 20 to 40 days after the start of treatment. The hazard type for both opioids was classified as early failure. CONCLUSIONS: Our findings suggest that elderly CNCP patients should be closely monitored after the start of opioid treatment, especially during the first week and, if possible, for 1 month, even if starting doses are within ranges recommended by the manufacturer and guidelines.

Effect of Remimazolam Tosilate on Respiratory Depression in Elderly Patients Undergoing Gastroscopy: A Multicentered, Prospective, and Randomized Study.

Background: Remimazolam tosilate (RT) is a new type of γ-aminobutyric acid subtype A (GABAA) receptor agonist, having the possibility to be an ideal sedative drug for procedural sedation. At present, there are few studies on the effect of RT on respiratory depression in elderly patients. We aimed to evaluate the effect of RT on respiratory depression in elderly patients undergoing gastroscopy. Methods: This prospective, randomized, single-blinded trial recruited patients from eight centers in China between May 2022 and July 2022. A total of 346 elderly patients undergoing gastroscopy were randomly divided into RT group (0.2 mg/kg) or propofol group (1.5 mg/kg), respectively. The primary outcome was the incidence of respiratory depression. Secondary outcomes include the incidence of sedative-related adverse events, the success rate of sedation, time to fully alert, time to loss of consciousness (LOC), time to ready for discharge, as well as the the patients, endoscopists and anethetists' satisfaction. Results: The incidence of respiratory depression was significantly reduced in the RT group compared with the propofol group (9.8% vs 17.9%, P=0.042). The time of LOC and fully alert in the RT group were longer than that in the propofol group (P < 0.05). The incidences of hypotention (50.9% vs 32.4%, P=0.001) and hypotension requiring treatment (5.8% vs 1.7%, P=0.031) were significantly higher in the propofol group than that in the RT group. The incidence and severity of injection pain were more frequently recorded in the propofol group than that in the RT group (40.5% vs 12.1%, P<0.05). There were no statistically significant differences between the two groups in terms of sedation success rates, time to ready for discharge, endoscopists and anethetists' satisfaction and other sedative-related adverse events. Conclusion: RT may be a suitable alternative sedative agent for elderly patients undergoing gastroscopy due to its safety profile.

Enfortumab vedotin-related pneumonitis is more common than expected and could lead to acute respiratory failure.

PURPOSE: To analyse the incidence of pneumonitis related to enfortumab vedotin (EV) in patients with metastatic urothelial cell carcinoma (mUC). METHODS: Patients with mUC who participated in two EV clinical trials in South Korea were analysed for the incidence and clinical course of EV-related pneumonitis through retrospective, independent review. The clinical characteristics and radiologic attributes of potential pneumonitis were identified and reviewed by the participating investigators and pulmonologists. RESULTS: Between October 2018 and January 2020, 64 patients were enrolled in the EV-201 and EV-301 trials across eight institutions in South Korea and were treated with EV. Among them, 18 (28.1%) developed all-grade EV-related pneumonitis, from which 2 (11.1%) patients died. The median time between the last dosing of immunotherapy and the start of EV was 5.6 weeks (range, 0.71-143.1). The median time from the start of EV treatment to the onset of pneumonitis was 13 weeks (range, 2.7-51.0). Of the patients who developed pneumonitis, 7 (38.9%) were clinically asymptomatic. The most common radiologic finding was organising pneumonia (66.7%). CONCLUSIONS: Although we could not rule out the relationship with prior immunotherapy administration, EV-related pneumonitis occurred in approximately 25% of the patients who had received EV in two prospective clinical trials, from which two died. Clinicians should closely monitor patients who have experienced immunotherapy treatment failure for the development of pneumonitis. A delay between initiating EV after termination of immunotherapy should be considered with caution.

Outcomes and risk factors for delayed-onset postoperative respiratory failure: a multi-center case-control study by the University of California Critical Care Research Collaborative (UC3RC).

BACKGROUND: Few interventions are known to reduce the incidence of respiratory failure that occurs following elective surgery (postoperative respiratory failure; PRF). We previously reported risk factors associated with PRF that occurs within the first 5 days after elective surgery (early PRF; E-PRF); however, PRF that occurs six or more days after elective surgery (late PRF; L-PRF) likely represents a different entity. We hypothesized that L-PRF would be associated with worse outcomes and different risk factors than E-PRF. METHODS: This was a retrospective matched case-control study of 59,073 consecutive adult patients admitted for elective non-cardiac and non-pulmonary surgical procedures at one of five University of California academic medical centers between October 2012 and September 2015. We identified patients with L-PRF, confirmed by surgeon and intensivist subject matter expert review, and matched them 1:1 to patients who did not develop PRF (No-PRF) based on hospital, age, and surgical procedure. We then analyzed risk factors and outcomes associated with L-PRF compared to E-PRF and No-PRF. RESULTS: Among 95 patients with L-PRF, 50.5% were female, 71.6% white, 27.4% Hispanic, and 53.7% Medicare recipients; the median age was 63 years (IQR 56, 70). Compared to 95 matched patients with No-PRF and 319 patients who developed E-PRF, L-PRF was associated with higher morbidity and mortality, longer hospital and intensive care unit length of stay, and increased costs. Compared to No-PRF, factors associated with L-PRF included: preexisiting neurologic disease (OR 4.36, 95% CI 1.81-10.46), anesthesia duration per hour (OR 1.22, 95% CI 1.04-1.44), and maximum intraoperative peak inspiratory pressure per cm H20 (OR 1.14, 95% CI 1.06-1.22). CONCLUSIONS: We identified that pre-existing neurologic disease, longer duration of anesthesia, and greater maximum intraoperative peak inspiratory pressures were associated with respiratory failure that developed six or more days after elective surgery in adult patients (L-PRF). Interventions targeting these factors may be worthy of future evaluation.