Update to the study protocol for an implementation-effectiveness trial comparing two education strategies for improving the uptake of noninvasive ventilation in patients with severe COPD exacerbation.

BACKGROUND: There is strong evidence that noninvasive ventilation (NIV) improves the outcomes of patients hospitalized with severe COPD exacerbation, and NIV is recommended as the first-line therapy for these patients. Yet, several studies have demonstrated substantial variation in NIV use across hospitals, leading to preventable morbidity and mortality. In addition, prior studies suggested that efforts to increase NIV use in COPD need to account for the complex and interdisciplinary nature of NIV delivery and the need for team coordination. Therefore, our initial project aimed to compare two educational strategies: online education (OLE) and interprofessional education (IPE), which targets complex team-based care in NIV delivery. Due to the impact of the COVID-19 pandemic on recruitment and planned intervention, we had made several changes in the study design, statistical analysis, and implementation strategies delivery as outlined in the methods. METHODS: We originally proposed a two-arm, pragmatic, cluster, randomized hybrid implementation-effectiveness trial comparing two education strategies to improve NIV uptake in patients with severe COPD exacerbation in 20 hospitals with a low baseline rate of NIV use. Due to logistical constrains and slow recruitment, we changed the study design to an opened cohort stepped-wedge design with three steps which will allow the institutions to enroll when they are ready to participate. Only the IPE strategy will be implemented, and the education will be provided in an online virtual format. Our primary outcome will be the hospital-level risk-standardized NIV proportion for the period post-IPE training, along with the change in rate from the period prior to training. Aim 1 will compare the change over time of NIV use among patients with COPD in the step-wedged design. Aim 2 will explore the mediators' role (respiratory therapist autonomy and team functionality) on the relationship between the implementation strategies and effectiveness. Finally, in Aim 3, through interviews with providers, we will assess the acceptability and feasibility of the educational training. CONCLUSION: The changes in study design will result in several limitation. Most importantly, the hospitals in the three cohorts are not randomized as they enroll based on their readiness. Second, the delivery of the IPE is virtual, and it is not known if remote education is conducive to team building. However, this study will be among the first to test the impact of IPE in the inpatient setting carefully and may generalize to other interventions directed to seriously ill patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT04206735 . Registered on December 20, 2019.

Prevention of invasive ventilation (PRiVENT)-a prospective, mixed-methods interventional, multicentre study with a parallel comparison group: study protocol.

BACKGROUND: Invasive mechanical ventilation (IMV) is a standard therapy for intensive care patients with respiratory failure. With increasing population age and multimorbidity, the number of patients who cannot be weaned from IMV increases, resulting in impaired quality of life and high costs. In addition, human resources are tied up in the care of these patients. METHODS: The PRiVENT intervention is a prospective, mixed-methods interventional, multicentre study with a parallel comparison group selected from insurance claims data of the health insurer Allgemeine Ortskrankenkasse Baden-Württemberg (AOK-BW) conducted in Baden-Württemberg, Germany, over 24 months. Four weaning centres supervise 40 intensive care units (ICUs), that are responsible for patient recruitment. The primary outcome, successful weaning from IMV, will be evaluated using a mixed logistic regression model. Secondary outcomes will be evaluated using mixed regression models. DISCUSSION: The overall objective of the PRiVENT project is the evaluation of strategies to prevent long-term IMV. Additional objectives aim to improve weaning expertise in and cooperation with the adjacent Intensive Care Units. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov (NCT05260853).

Update on the management of acute respiratory failure using non-invasive ventilation and pulse oximetry.

This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2023. Other selected articles can be found online at  https://www.biomedcentral.com/collections/annualupdate2023 . Further information about the Annual Update in Intensive Care and Emergency Medicine is available from  https://link.springer.com/bookseries/8901 .

Physiometric Response to High-Flow Nasal Cannula Support in Acute Bronchiolitis.

OBJECTIVES: To describe the rate of high-flow nasal cannula (HFNC) nonresponse and paired physiometric responses (changes [∆] in heart rate [HR] and respiratory rate [RR]) before and after HFNC initiation in hospitalized children with bronchiolitis. METHODS: We performed a single-center, prospective descriptive study in a PICU within a quaternary referral center, assessing children aged ≤2 years admitted for bronchiolitis on HFNC from November 2017 to March 2020. We excluded for cystic fibrosis, airway anomalies, pulmonary hypertension, tracheostomy, neuromuscular disease, congenital heart disease, or preadmission intubation. Primary outcomes were paired ∆ and %∆ in HR and RR before and after HFNC initiation. Secondary outcomes were HFNC nonresponse rate (ie, intubation or transition to noninvasive positive pressure ventilation). Analyses included χ2, Student's t, Wilcoxon rank, and paired testing. RESULTS: Of the 172 children studied, 56 (32.6%) experienced HFNC nonresponse at a median of 14.4 (interquartile range: 4.8-36) hours and 11 (6.4%) were intubated. Nonresponders had a greater frequency of bacterial pneumonia, but otherwise no major differences in demographics, comorbidities, or viral pathogens were noted. Responders experienced reductions in both %ΔRR (-17.1% ± 15.8% vs +5.3% ± 22.3%) and %ΔHR (-6.5% ± 10.5% vs 0% ± 10.9%) compared with nonresponders. CONCLUSIONS: In this prospective, observational cohort study, we provide baseline data describing expected physiologic changes after initiation of HFNC for children admitted to the PICU for bronchiolitis. In our descriptive analysis, patients with comorbid bacterial pneumonia appear to be at additional risk for subsequent HFNC nonresponse.

Prolonged non-invasive respiratory supports in a COVID-19 patient with severe acute hypoxemic respiratory failure.

A pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 was declared in 2020. Severe cases were characterized by the development of acute hypoxemic respiratory failure (AHRF) requiring advanced respiratory support. However, intensive care units (ICU) were saturated, and many patients had to be treated out of ICU. This case describes a 75-year-old man affected by AHRF due to Coronavirus Disease 2019 (COVID-19), hospitalized in a high-dependency unit, with PaO2/FiO2 <100 for 28 consecutive days. An experienced team with respiratory physiotherapists was in charge of the noninvasive ventilatory support (NIVS). The patient required permanent NIVS with continuous positive airway pressure, non-invasive ventilation, high flow nasal oxygen and body positioning. He was weaned from NIVS after 37 days and started exercise training afterwards. The patient was discharged at home with low-flow oxygen therapy. This case represents an example of a successful treatment of AHRF with the still controversial noninvasive respiratory support in one patient with COVID-19.

Initial Observations of COVID-19 in US Children.

Coronavirus disease (COVID-19) has affected children differently from adults worldwide. Data on the clinical presentation of the infection in children are limited. We present a detailed account of pediatric inpatients infected with severe acute respiratory syndrome coronavirus 2 virus at our institution during widespread local transmission, aiming to understand disease presentation and outcomes. A retrospective chart review was performed of children, ages 0 to 18 years, with a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2 on nasopharyngeal specimens admitted to our hospital over a 4-week period. We present clinical data from 22 patients and highlight the variability of the presentation. In our study, most children presented without respiratory illness or symptoms suggestive of COVID-19; many were identified only because of universal testing. Because children may have variable signs and symptoms of COVID-19 infection, targeted testing may miss some cases.

Effect of postextubation noninvasive ventilation with active humidification vs high-flow nasal cannula on reintubation in patients at very high risk for extubation failure: a randomized trial.

PURPOSE: High-flow nasal cannula (HFNC) oxygen therapy was noninferior to noninvasive ventilation (NIV) for preventing reintubation in a heterogeneous population at high-risk for extubation failure. However, outcomes might differ in certain subgroups of patients. Thus, we aimed to determine whether NIV with active humidification is superior to HFNC in preventing reintubation in patients with ≥ 4 risk factors (very high risk for extubation failure). METHODS: Randomized controlled trial in two intensive care units in Spain (June 2020‒June 2021). Patients ready for planned extubation with ≥ 4 of the following risk factors for reintubation were included: age > 65 years, Acute Physiology and Chronic Health Evaluation II score > 12 on extubation day, body mass index > 30, inadequate secretions management, difficult or prolonged weaning, ≥ 2 comorbidities, acute heart failure indicating mechanical ventilation, moderate-to-severe chronic obstructive pulmonary disease, airway patency problems, prolonged mechanical ventilation, or hypercapnia on finishing the spontaneous breathing trial. Patients were randomized to undergo NIV with active humidification or HFNC for 48 h after extubation. The primary outcome was reintubation rate within 7 days after extubation. Secondary outcomes included postextubation respiratory failure, respiratory infection, sepsis, multiorgan failure, length of stay, mortality, adverse events, and time to reintubation. RESULTS: Of 182 patients (mean age, 60 [standard deviation (SD), 15] years; 117 [64%] men), 92 received NIV and 90 HFNC. Reintubation was required in 21 (23.3%) patients receiving NIV vs 35 (38.8%) of those receiving HFNC (difference -15.5%; 95% confidence interval (CI) -28.3 to -1%). Hospital length of stay was lower in those patients treated with NIV (20 [12‒36.7] days vs 26.5 [15‒45] days, difference 6.5 [95%CI 0.5-21.1]). No additional differences in the other secondary outcomes were observed. CONCLUSIONS: Among adult critically ill patients at very high-risk for extubation failure, NIV with active humidification was superior to HFNC for preventing reintubation.

Long-term outcomes of patients with COVID-19 treated with helmet noninvasive ventilation or usual respiratory support: follow-up study of the Helmet-COVID randomized clinical trial.

PURPOSE: To evaluate whether helmet noninvasive ventilation compared to usual respiratory support reduces 180-day mortality and improves health-related quality of life (HRQoL) in patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia. METHODS: This is a pre-planned follow-up study of the Helmet-COVID trial. In this multicenter, randomized clinical trial, adults with acute hypoxemic respiratory failure (n = 320) due to coronavirus disease 2019 (COVID-19) were randomized to receive helmet noninvasive ventilation or usual respiratory support. The modified intention-to-treat population consisted of all enrolled patients except three who were lost at follow-up. The study outcomes were 180-day mortality, EuroQoL (EQ)-5D-5L index values, and EQ-visual analog scale (EQ-VAS). In the modified intention-to-treat analysis, non-survivors were assigned a value of 0 for EQ-5D-5L and EQ-VAS. RESULTS: Within 180 days, 63/159 patients (39.6%) died in the helmet noninvasive ventilation group compared to 65/158 patients (41.1%) in the usual respiratory support group (risk difference - 1.5% (95% confidence interval [CI] - 12.3, 9.3, p = 0.78). In the modified intention-to-treat analysis, patients in the helmet noninvasive ventilation and the usual respiratory support groups did not differ in EQ-5D-5L index values (median 0.68 [IQR 0.00, 1.00], compared to 0.67 [IQR 0.00, 1.00], median difference 0.00 [95% CI - 0.32, 0.32; p = 0.91]) or EQ-VAS scores (median 70 [IQR 0, 93], compared to 70 [IQR 0, 90], median difference 0.00 (95% CI - 31.92, 31.92; p = 0.55). CONCLUSIONS: Helmet noninvasive ventilation did not reduce 180-day mortality or improve HRQoL compared to usual respiratory support among patients with acute hypoxemic respiratory failure due to COVID-19 pneumonia.

Helmet CPAP in the emergency department: A narrative review.

BACKGROUND: The choice of correct interface for the right patient is crucial for the success of non-invasive ventilation (NIV) therapy. Helmet CPAP is a type of interface used to deliver NIV. Helmet CPAP improves oxygenation by keeping the airway open throughout the breathing cycle with positive end-expiratory pressure (PEEP). OBJECTIVE: This narrative review describes the technical aspects and clinical indications of helmet continuous positive airway pressure (CPAP). In addition, we explore the advantages and challenges faced using this device at the Emergency Department (ED). DISCUSSION: Helmet CPAP is tolerable than other NIV interfaces, provides a good seal and has good airway stability. During Covid-19 pandemic, there are evidences it reduced the risk of aerosolization. The potential clinical benefit of helmet CPAP is demonstrated in acute cardiogenic pulmonary oedema (ACPO), Covid-19 pneumonia, immunocompromised patient, acute chest trauma and palliative patient. Compare to conventional oxygen therapy, helmet CPAP had been shown to reduce intubation rate and decrease mortality. CONCLUSION: Helmet CPAP is one of the potential NIV interface in patients with acute respiratory failure presenting to the emergency department. It is better tolerated for prolonged usage, reduced intubation rate, improved respiratory parameters, and offers protection against aerosolization in infectious diseases.

Validation of Sequential ROX-Index Score Beyond 12 Hours in Predicting Treatment Failure and Mortality in COVID-19 Patients Receiving Oxygen via High-Flow Nasal Cannula.

Background: High-flow nasal cannula (HFNC) is an oxygen delivery method shown to reduce the risk of intubation and mortality in patients with type 1 respiratory failure. The ROX-index score can predict HFNC failure. This study aims to evaluate sequential ROX-index assessments as predictors of HFNC failure and mortality. Methods: Prospective observational single-center study including all adult patients with positive SARS-CoV-2 PCR placed under HFNC from 1st November 2020 to 31st May 2021, and patients with hemodynamic instability or unable to tolerate HFNC were excluded. The primary endpoint was successful HFNC de-escalation. Results: In univariate analysis, HFNC de-escalation was associated with younger age (59.2 ± 14 vs. 67.7 ± 10.5 and p < 0.001), lower levels of serum lactate (1.1 vs. 1.5 and p=0.013), and higher ROX-index at 12 hrs (5.09 vs. 4.13 and p < 0.001). ROC curve analysis of ROX-index at 12 hrs yielded a c-statistic of 71.2% (95% CI 61.6-80.9 and p < 0.001). ROX-index at 12 hrs and age retained significance in multivariate analysis. Using an optimal cutoff point of 4.43, we calculated a sensitivity of 64.5% and specificity of 69.6%. In univariate survival analysis, older age (68.8 ± 9.7 vs. 58.9 ± 13.9 and p < 0.001), greater creatinine values (0.96 vs. 0.84 and p=0.022), greater SOFA score (p=0.039), and a lower 12 hrs ROX-index (4.22 vs. 4.95 and p=0.02) were associated with hospital mortality. The SOFA score and age retained significance in multivariate survival analysis. Conclusion: ROX-index is proven to be a valuable and easy-to-use tool for clinicians in the assessment of COVID-19 patients under HFNC.

Coronavirus Disease-2019 in Pregnancy.

Coronavirus disease-2019 (COVID-19) infection during pregnancy is associated with severe complications and adverse effects for the mother, the fetus, and the neonate. The frequency of these outcomes varies according to the region, the gestational age, and the presence of comorbidities. Many COVID-19 interventions, including oxygen therapy, high-flow nasal cannula, and invasive mechanical ventilation, are challenging and require understanding physiologic adaptations of pregnancy. Vaccination is safe during pregnancy and lactation and constitutes the most important intervention to reduce severe disease and complications.

Rising Mortality in Coronavirus-19 Patients Supported With Extracorporeal Membrane Oxygenation.

We aimed to describe practice patterns and outcomes in patients with extracorporeal membrane oxygenation (ECMO) support throughout the coronavirus 2019 (COVID-19) pandemic, with the hypothesis that mortality would improve as we accumulated knowledge and experience. We included 48 patients supported on veno-venous ECMO (VV-ECMO) at a single institution between April 2020 and December 2021. Patients were categorized into three waves based on cannulation date, corresponding to the wild-type (wave 1), alpha (wave 2), and delta (wave 3) variants. One hundred percent of patients in waves 2 and 3 received glucocorticoids, compared with 29% in wave 1 ( p < 0.01), and the majority received remdesivir (84% and 92% in waves 2 and 3, vs . 35% in wave 1; p < 0.01). Duration of pre-ECMO noninvasive ventilation was longer in waves 2 and 3 (mean 8.8 days and 3.9 days, vs . 0.7 days in wave 1; p < 0.01), as was time to cannulation (mean 17.2 and 14.6 days vs . 8.8 days in wave 1; p < 0.01) and ECMO duration (mean 55.7 days and 43.0 days vs . 28.4 days in wave 1; p = 0.02). Mortality in wave 1 was 35%, compared with 63% and 75% in waves 2 and 3 ( p = 0.05). These results suggest an increased prevalence of medically refractory disease and rising mortality in later variants of COVID-19.

Pneumothorax in hospitalized COVID-19 patients with severe respiratory failure: Risk factors and outcome.

PNX was described as an uncommon complication in COVID-19 patients but clinical risk predictors and the potential role in patient's outcome are still unclear. We assessed prevalence, risk predictors and mortality of PNX in hospitalized COVID- 19 with severe respiratory failure performing a retrospective observational analysis of 184 patients admitted to our COVID-19 Respiratory Unit in Vercelli from October 2020 to March 2021. We compared patients with and without PNX reporting prevalence, clinical and radiological features, comorbidities, and outcomes. Prevalence of PNX was 8.1% and mortality was >86% (13/15) significantly higher than in patients without PNX (56/169) (P < 0.001). PNX was more likely to occur in patients with a history of cognitive decline (HR: 31.18) who received non-invasive ventilation (NIV) (p < 0.0071) and with low P/F ratio (HR: 0.99, p = 0.004). Blood chemistry in the PNX subgroup compared to patients without PNX showed a significant increase in LDH (420 U/L vs 345 U/L, respectively p = 0.003), ferritin (1111 mg/dl vs 660 mg/dl, respectively p = 0.006) and decreased lymphocytes (HR: 4.440, p = 0.004). PNX may be associated with a worse prognosis in terms of mortality in COVID patients. Possible mechanisms may include the hyperinflammatory status associated with critical illness, the use of NIV, the severity of respiratory failure and cognitive impairment. We suggest, in selected patients showing low P/F ratio, cognitive impairment and metabolic cytokine storm, an early treatment of systemic inflammation in association with high-flow oxygen therapy as a safer alternative to NIV in order to avoid fatalities connected with PNX.

Mechanically Ventilated Patients With Coronavirus Disease 2019 Had a Higher Chance of In-Hospital Death If Treated With High-Flow Nasal Cannula Oxygen Before Intubation.

BACKGROUND: The impact of high-flow nasal cannula (HFNC) on outcomes of patients with respiratory failure from coronavirus disease 2019 (COVID-19) is unknown. We sought to assess whether exposure to HFNC before intubation was associated with successful extubation and in-hospital mortality compared to patients receiving intubation only. METHODS: This single-center retrospective study examined patients with COVID-19-related respiratory failure from March 2020 to March 2021 who required HFNC, intubation, or both. Data were abstracted from the electronic health record. Use and duration of HFNC and intubation were examined' as well as demographics and clinical characteristics. We assessed the association between HFNC before intubation (versus without) and chance of successful extubation and in-hospital death using Cox proportional hazards models adjusting for age, sex, race/ethnicity, obesity, hypertension, diabetes, prior chronic obstructive pulmonary disease or asthma, HCO 3 , CO 2 , oxygen-saturation-to-inspired-oxygen (S:F) ratio, pulse, respiratory rate, temperature, and length of stay before intervention. RESULTS: A total of n = 440 patients were identified, of whom 311 (70.7%) received HFNC before intubation, and 129 (29.3%) were intubated without prior use of HFNC. Patients who received HFNC before intubation had a higher chance of in-hospital death (hazard ratio [HR], 2.08; 95% confidence interval [CI], 1.06-4.05). No difference was found in the chance of successful extubation between the 2 groups (0.70, 0.41-1.20). CONCLUSIONS: Among patients with respiratory failure from COVID-19 requiring mechanical ventilation, patients receiving HFNC before intubation had a higher chance of in-hospital death. Decisions on initial respiratory support modality should weigh the risks of intubation with potential increased mortality associated with HFNC.