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.

Predicting the successful application of high-flow nasal oxygen cannula in patients with COVID-19 respiratory failure: a retrospective analysis.

BACKGROUND: The right time of high-flow nasal cannulas (HFNCs) application in COVID-19 patients with acute respiratory failure remains uncertain. RESEARCH DESIGN AND METHODS: In this retrospective study, COVID-19-infected adult patients with hypoxemic respiratory failure were enrolled. Their baseline epidemiological data and respiratory failure related parameters, including the Ventilation in COVID-19 Estimation (VICE), and the ratio of oxygen saturation (ROX index), were recorded. The primary outcome measured was the 28-day mortality. RESULTS: A total of 69 patients were enrolled. Fifty-four (78%) patients who intubated and received invasive mechanical ventilatory (MV) support on day 1 were enrolled in the MV group. The remaining fifteen (22%) patients received HFNC initially (HFNC group), in which, ten (66%) patients were not intubated during hospitalization were belong to HFNC-success group and five (33%) of these patients were intubated later due to disease progression were attributed to HFNC-failure group. Compared with those in the MV group, those in the HFNC group had a lower mortality rate (6.7% vs. 40.7%, p = 0.0138). There were no differences in baseline characteristics among the two groups; however, the HFNC group had a lower VICE score (0.105 [0.049-0.269] vs. 0.260 [0.126-0.693], p = 0.0092) and higher ROX index (5.3 [5.1-10.7] vs. 4.3 [3.9-4.9], p = 0.0007) than the MV group. The ROX index was higher in the HFNC success group immediately before (p = 0.0136) and up to 12 hours of HFNC therapy than in the HFNC failure group. CONCLUSIONS: Early intubation may be considered in patients with a higher VICE score or a lower ROX index. The ROX score during HFNCs use can provide an early warning sign of treatment failure. Further investigations are warranted to confirm these results.

High flow nasal cannulas (HFNCs) were widely used in patients with COVID-19 infection related hypoxemic respiratory failure. However, there were concerns about its failure and related delayed intubation may be associated with a higher mortality rate. This retrospective study revealed patients with higher baseline disease severity and higher VICE scores may be treated with primary invasive mechanical ventilation. On the contrary, if their baseline VICE score is low and ROX index is high, HFNCs treatment might be safely applied initially. The trends of serial ROX index values during HFNC use could be a reliable periscope to predict the HFNC therapy outcome, therefore avoided delayed intubation.

High-flow nasal cannula reduces intubation rate in patients with COVID-19 with acute respiratory failure: a meta-analysis and systematic review.

OBJECTIVE: This study aimed to investigate the effect of high-flow nasal cannula therapy (HFNC) versus conventional oxygen therapy (COT) on intubation rate, 28-day intensive care unit (ICU) mortality, 28-day ventilator-free days (VFDs) and ICU length of stay (ICU LOS) in adult patients with acute respiratory failure (ARF) associated with COVID-19. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Web of Science, Cochrane Library and Embase up to June 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Only randomised controlled trials or cohort studies comparing HFNC with COT in patients with COVID-19 were included up to June 2022. Studies conducted on children or pregnant women, and those not published in English were excluded. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently screened the titles, abstracts and full texts. Relevant information was extracted and curated in the tables. The Cochrane Collaboration tool and Newcastle-Ottawa Scale were used to assess the quality of randomised controlled trials or cohort studies. Meta-analysis was conducted using RevMan V.5.4 computer software using a random effects model with a 95% CI. Heterogeneity was assessed using Cochran's Q test (χ2) and Higgins I2 statistics, with subgroup analyses to account for sources of heterogeneity. RESULTS: Nine studies involving 3370 (1480 received HFNC) were included. HFNC reduced the intubation rate compared with COT (OR 0.44, 95% CI 0.28 to 0.71, p=0.0007), decreased 28-day ICU mortality (OR 0.54, 95% CI 0.30 to 0.97, p=0.04) and improved 28-day VFDs (mean difference (MD) 2.58, 95% CI 1.70 to 3.45, p<0.00001). However, HFNC had no effect on ICU LOS versus COT (MD 0.52, 95% CI -1.01 to 2.06, p=0.50). CONCLUSIONS: Our study indicates that HFNC may reduce intubation rate and 28-day ICU mortality, and improve 28-day VFDs in patients with ARF due to COVID-19 compared with COT. Large-scale randomised controlled trials are necessary to validate our findings. PROSPERO REGISTRATION NUMBER: CRD42022345713.

Correlation of important prognostic factors and CT scores in invasive and non-invasive ventilation of COVID-19 patients.

BACKGROUND: Intensive care workers received the largest share of the COVID-19 pandemic, which caused nightmares to the whole world. In COVID-19 pneumonia cases which had high mortality rates, many prognostic factors and laboratory examinations were tried to evaluate the clinical severity quickly and accurately.This study was planned to investigate a correlation between the initially ventilation strategy and major prognostic parameters and CT scores in patients admitted to intensive care unit (ICU). METHODS: In our study, we reviewed 50 consecutive non-invasive mv and 50 consecutive invasive mv treatment of COVID-19 pneumonia patients between March 23, 2020,and May 23, 2020, in the ICUs of our hospital. Patients who were divided into twogroups (non-invasive mechanical ventilation [NIMV] and invasive mechanical ventilation [IMV]) as an initial ventilation strategy according to clinical severity and P/F ratios were evaluated comparatively; demographic data, admission and lowest P/F ratios, admission and highest SOFA scores, comorbidity status, scores on CT at diagnosis, length of ICU stays, hospitalization periods, and mortality rates were examined. RESULTS: About 85% of all patients were 46 years and older. No significant difference was found in terms of gender and comorbidity status. The lowest P/F ratio was significantly lower in IMV group. The admission and highest SOFA values were higher in the IMV group. There was no significant difference between the CT scores and the number of lobes involved. The mortality rate in the IMV group was significantly higher. CONCLUSION: Patients who started treatment with NIMV had relatively low poor prognostic factors, their mortality was lower. However, the total CT score at diagnosis was expected to be higher in those who were performed IMV, no significant difference was found in our study. We concluded that the severity classification of the patients cannot be made according to CT scores. CT results should be evaluated as a whole according to the patient's clinic, predisposing factors, and response to treatment.

How long is too long: A retrospective study evaluating the impact of the duration of noninvasive oxygenation support strategies (high flow nasal cannula & BiPAP) on mortality in invasive mechanically ventilated patients with COVID-19.

BACKGROUND/AIM: We investigated the association of noninvasive oxygenation support [high flow nasal cannula (HFNC) and BiPAP], timing of invasive mechanical ventilation (IMV), and inpatient mortality among patients hospitalized with COVID-19. METHODS: Retrospective chart review study of patients hospitalized with COVID-19 (ICD-10 code U07.1) and received IMV from March 2020-October 2021. Charlson comorbidity index (CCI) was calculated; Obesity defined as body mass index (BMI) ≥ 30 kg/m2; morbid obesity was BMI ≥ 40 kg/m2. Clinical parameters/vital signs recorded at time of admission. RESULTS: 709 COVID-19 patients underwent IMV, predominantly admitted from March-May 2020 (45%), average age 62±15 years, 67% male, 37% Hispanic, and 9% from group living settings. 44% had obesity, 11% had morbid obesity, 55% had type II diabetes, 75% had hypertension, and average CCI was 3.65 (SD = 3.11). Crude mortality rate was 56%. Close linear association of age with inpatient-mortality risk was found [OR (95% CI) = 1.35 (1.27-1.44) per 5 years, p<0.0001)]. Patients who died after IMV received noninvasive oxygenation support significantly longer: 5.3 (8.0) vs. 2.7 (SD 4.6) days; longer use was also independently associated with a higher risk of inpatient-mortality: OR = 3.1 (1.8-5.4) for 3-7 days, 7.2 (3.8-13.7) for ≥8 days (reference: 1-2 days) (p<0.0001). The association magnitude varied between age groups: 3-7 days duration (ref: 1-2 days), OR = 4.8 (1.9-12.1) in ≥65 years old vs. 2.1 (1.0-4.6) in <65 years old. Higher mortality risk was associated with higher CCI in patients ≥65 (P = 0.0082); among younger patients, obesity (OR = 1.8 (1.0-3.2) or morbid obesity (OR = 2.8;1.4-5.9) (p<0.05) were associated. No mortality association was found for sex or race. CONCLUSION: Time spent on noninvasive oxygenation support [as defined by high flow nasal cannula (HFNC) and BiPAP] prior to IMV increased mortality risk. Research for the generalizability of our findings to other respiratory failure patient populations is needed.

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.

Nasopharyngeal SARS-CoV-2 may not be dispersed by a high-flow nasal cannula.

A high-flow nasal cannula (HFNC) therapy plays a significant role in providing respiratory support to critically ill patients with coronavirus disease 2019 (COVID-19); however, the dispersion of the virus owing to aerosol generation is a matter of concern. This study aimed to evaluate if HFNC disperses the virus into the air. Among patients with COVID-19 admitted to private rooms with controlled negative pressure, we enrolled those admitted within 10 days of onset and requiring oxygenation through a conventional nasal cannula or HFNC therapy. Of the 17 patients enrolled, we obtained 22 samples (11 in the conventional nasal cannula group and 11 in the HFNC group). Viral RNA was detected in 20 nasopharyngeal swabs, and viable viruses were isolated from three nasopharyngeal swabs. Neither viral RNA nor viable virus was detected in the air sample at 0.5 m regardless of the oxygen-supplementation device. We detected viral RNA in two samples in the conventional nasal cannula group but not in the HFNC therapy group in gelatin filters located 3 m from the patient and the surface of the ventilation. This study directly demonstrated that despite viral RNA detection in the nasopharynx, viruses may not be dispersed by HFNC therapy. This warrants further research to determine if similar results can be obtained under different conditions.

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.