Switches in non-invasive respiratory support strategies during acute hypoxemic respiratory failure: Need to monitoring from a retrospective observational study.

OBJECTIVE: To explore combined non-invasive-respiratory-support (NIRS) patterns, reasons for NIRS switching, and their potential impact on clinical outcomes in acute-hypoxemic-respiratory-failure (AHRF) patients. DESIGN: Retrospective, single-center observational study. SETTING: Intensive Care Medicine. PATIENTS: AHRF patients (cardiac origin and respiratory acidosis excluded) underwent combined NIRS therapies such as non-invasive-ventilation (NIV) and High-Flow-Nasal-Cannula (HFNC). INTERVENTIONS: Patients were classified based on the first NIRS switch performed (HFNC-to-NIV or NIV-to-HFNC), and further specific NIRS switching strategies (NIV trial-like vs. Non-NIV trial-like and single vs. multiples switches) were independently evaluated. MAIN VARIABLES OF INTEREST: Reasons for switching, NIRS failure and mortality rates. RESULTS: A total of 63 patients with AHRF were included, receiving combined NIRS, 58.7% classified in the HFNC-to-NIV group and 41.3% in the NIV-to-HFNC group. Reason for switching from HFNC to NIV was AHRF worsening (100%), while from NIV to HFNC was respiratory improvement (76.9%). NIRS failure rates were higher in the HFNC-to-NIV than in NIV-to-HFNC group (81% vs. 35%, p < 0.001). Among HFNC-to-NIV patients, there was no difference in the failure rate between the NIV trial-like and non-NIV trial-like groups (86% vs. 78%, p = 0.575) but the mortality rate was significantly lower in NIV trial-like group (14% vs. 52%, p = 0.02). Among NIV to HFNC patients, NIV failure was lower in the single switch group compared to the multiple switches group (15% vs. 53%, p = 0.039), with a shorter length of stay (5 [2-8] vs. 12 [8-30] days, p = 0.001). CONCLUSIONS: NIRS combination is used in real life and both switches' strategies, HFNC to NIV and NIV to HFNC, are common in AHRF management. Transitioning from HFNC to NIV is suggested as a therapeutic escalation and in this context performance of a NIV-trial could be beneficial. Conversely, switching from NIV to HFNC is suggested as a de-escalation strategy that is deemed safe if there is no NIRS failure.

Comparing lung aeration and respiratory effort using two different spontaneous breathing trial: T-piece vs pressure support ventilation.

OBJECTIVE: To assess the changes in lung aeration and respiratory effort generated by two different spontaneous breathing trial (SBT): T-piece (T-T) vs pressure support ventilation (PSV). DESIGN: Prospective, interventionist and randomized study. SETTING: Intensive Care Unit (ICU) of Hospital del Mar. PARTICIPANTS: Forty-three ventilated patients for at least 24 h and considered eligible for an SBT were included in the study between October 2017 and March 2020. INTERVENTIONS: 30-min SBT with T-piece (T-T group, 20 patients) or 8-cmH2O PSV and 5-cmH2O positive end expiratory pressure (PSV group, 23 patients). MAIN VARIABLES OF INTEREST: Demographics, clinical data, physiological variables, lung aeration evaluated with electrical impedance tomography (EIT) and lung ultrasound (LUS), and respiratory effort using diaphragmatic ultrasonography (DU) were collected at different timepoints: basal (BSL), end of SBT (EoSBT) and one hour after extubation (OTE). RESULTS: There were a loss of aeration measured with EIT and LUS in the different study timepoints, without statistical differences from BSL to OTE, between T-T and PSV [LUS: 3 (1, 5.5) AU vs 2 (1, 3) AU; p = 0.088; EELI: -2516.41 (-5871.88, 1090.46) AU vs -1992.4 (-3458.76, -5.07) AU; p = 0.918]. Percentage of variation between BSL and OTE, was greater when LUS was used compared to EIT (68.1% vs 4.9%, p ≤ 0.001). Diaphragmatic excursion trend to decrease coinciding with a loss of aeration during extubation. CONCLUSION: T-T and PSV as different SBT strategies in ventilated patients do not show differences in aeration loss, nor estimated respiratory effort or tidal volume measured by EIT, LUS and DU.

Effectiveness of diaphragmatic ultrasound as a predictor of successful weaning from mechanical ventilation: a systematic review and meta-analysis.

BACKGROUND: Several measurements have been used to predict the success of weaning from mechanical ventilation; however, their efficacy varies in different studies. In recent years, diaphragmatic ultrasound has been used for this purpose. We conducted a systematic review and meta-analysis to evaluate the effectiveness of diaphragmatic ultrasound in predicting the success of weaning from mechanical ventilation. METHODS: Two investigators independently searched PUBMED, TRIP, EMBASE, COCHRANE, SCIENCE DIRECT, and LILACS for articles published between January 2016 and July 2022. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 tool; additionally, the certainty of the evidence is evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. Sensitivity and specificity analysis was performed for diaphragmatic excursion and diaphragmatic thickening fraction; positive and negative likelihood ratios and diagnostic odds ratios (DOR) with their confidence intervals (95% CI) were calculated by random effects analysis, summary receiver operating characteristic curve was estimated. Sources of heterogeneity were explored by subgroup analysis and bivariate meta-regression. RESULTS: Twenty-six studies were included, of which 19 were included in the meta-analysis (1204 patients). For diaphragmatic excursion, sensitivity was 0.80 (95% CI 0.77-0.83), specificity 0.80 (95% CI 0.75-0.84), area under the summary receiver operating characteristic curve 0.87 and DOR 17.1 (95% CI 10.2-28.6). For the thickening fraction, sensitivity was 0.85 (95% CI 0.82-0.87), specificity 0.75 (95% CI 0.69-0.80), area under the summary receiver operating characteristic curve 0.87 and DOR 17.2 (95% CI 9.16-32.3). There was heterogeneity among the included studies. When performing a subgroup analysis and excluding studies with atypical cutoff values, sensitivity and specificity increased for diaphragmatic thickening fraction; sensitivity increased and specificity decreased for diaphragmatic excursion; when comparing studies using pressure support (PS) versus T-tube, there was no significant difference in sensitivity and specificity; bivariate meta-regression analysis shows that patient position at the time of testing was a factor of heterogeneity in the included studies. CONCLUSIONS: Measurement of diaphragmatic excursion and diaphragmatic thickening fraction predict the probability of successful weaning from mechanical ventilation with satisfactory diagnostic accuracy; however, significant heterogeneity was evident in the different included studies. Studies of high methodological quality in specific subgroups of patients in intensive care units are needed to evaluate the role of diaphragmatic ultrasound as a predictor of weaning from mechanical ventilation.

Association between histological diaphragm atrophy and ultrasound diaphragm expiratory thickness in ventilated patients.

BACKGROUND: Diaphragm fiber atrophy has been evidenced after short periods of mechanical ventilation (MV) and related to critical illness-associated diaphragm weakness. Atrophy is described as a decrease in diaphragm fiber cross-sectional area (CSA) in human diaphragm biopsy, but human samples are still difficult to obtain in clinics. In recent years, ultrasound has become a useful tool in intensive care to evaluate diaphragm anatomy. The present study aimed to evaluate the ability of diaphragm expiratory thickness (Tdi) measured by ultrasound to predict diaphragm atrophy, defined by a decrease in diaphragm fiber CSA obtained through diaphragm biopsy (the gold standard technique) in ventilated patients. METHODS: Diaphragm biopsies and diaphragm ultrasound were performed in ventilated donors and in control subjects. Demographic variables, comorbidities, severity on admission, treatment, laboratory test results and evolution variables were evaluated. Immunohistochemical analysis to determine CSA and ultrasound measurements of Tdi at end-expiration were performed, and median values of the control group were used as thresholds to determine agreement between them in further analysis. Sensitivity, specificity, and positive and negative predictive values of an ultrasound Tdi cutoff for detecting histologic atrophy were calculated. Agreement between two ultrasound observers was also assessed. RESULTS: Thirty-five ventilated organ donors and 5 ventilated controls were included, without differences in basic characteristics. CSA and Tdi were lower in donors than in controls. All donors presented lower CSA, but only 74% lower Tdi regarding control group thresholds. The cut-off value for lower diaphragm expiratory thickness (Tdi < 1.7 mm) presented a sensitivity of 73%, a specificity of 67%, a positive predictive value of 96% and a negative predictive value of 17% for determining the presence of diaphragm atrophy (CSA < 2851 µm2). CONCLUSIONS: Diaphragm atrophy and thickness reduction is associated to MV. While a lower Tdi in diaphragm ultrasound is a good tool for diagnosing atrophy, normal or increased Tdi cannot rule atrophy out showing that both parameters should not be considered as synonymous.

Metabolic Signatures Associated with Severity in Hospitalized COVID-19 Patients.

The clinical evolution of COVID-19 pneumonia is poorly understood. Identifying the metabolic pathways that are altered early with viral infection and their association with disease severity is crucial to understand COVID-19 pathophysiology, and guide clinical decisions. This study aimed at assessing the critical metabolic pathways altered with disease severity in hospitalized COVID-19 patients. Forty-nine hospitalized patients with COVID-19 pneumonia were enrolled in a prospective, observational, single-center study in Barcelona, Spain. Demographic, clinical, and analytical data at admission were registered. Plasma samples were collected within the first 48 h following hospitalization. Patients were stratified based on the severity of their evolution as moderate (N = 13), severe (N = 10), or critical (N = 26). A panel of 221 biomarkers was measured by targeted metabolomics in order to evaluate metabolic changes associated with subsequent disease severity. Our results show that obesity, respiratory rate, blood pressure, and oxygen saturation, as well as some analytical parameters and radiological findings, were all associated with disease severity. Additionally, ceramide metabolism, tryptophan degradation, and reductions in several metabolic reactions involving nicotinamide adenine nucleotide (NAD) at inclusion were significantly associated with respiratory severity and correlated with inflammation. In summary, assessment of the metabolomic profile of COVID-19 patients could assist in disease severity stratification and even in guiding clinical decisions.

Incidence of pulmonary embolism in patients with non-invasive respiratory support during COVID-19 outbreak.

While the incidence of thrombotic complications in critically ill patients is very high, in patients under non-invasive respiratory support (NIS) is still unknown. The specific incidence of thrombotic events in each of the clinical scenarios within the broad spectrum of severity of COVID-19, is not clearly established, and this has not allowed the implementation of thromboprophylaxis or anticoagulation for routine care in COVID-19. Patients admitted in a semi-critical unit treated initially with NIS, especially Continuous-Positive Airway Pressure (CPAP), were included in the study. The cumulative incidence of pulmonary embolism was analyzed and compared between patients with good response to NIS and patients with clinical deterioration that required orotracheal intubation. 93 patients were included and 16% required mechanical ventilation (MV) after the NIS. The crude cumulative incidence of the PE was 14% (95%, CI 8-22) for all group. In patients that required orotracheal intubation and MV, the cumulative incidence was significantly higher [33% (95%, CI 16-58)] compared to patients that continued with non-invasive support [11% (CI 5-18)] (Log-Rank, p = 0.013). Patients that required mechanical ventilation were at higher risk of PE for a HR of 4.3 (95%CI 1.2-16). In conclusion, cumulative incidence of PE is remarkably higher in critically patients with a potential impact in COVID-19 evolution. In this context, patients under NIS are a very high-risk group for developing PE without a clear strategy regarding thromboprophylaxis.

Aeration changes induced by high flow nasal cannula are more homogeneous than those generated by non-invasive ventilation in healthy subjects.

BACKGROUND: Non-invasive mechanical ventilation (NIV) is a standard respiratory support technique used in intensive care units. High-Flow Nasal Cannula (HFNC) has emerged as an alternative, but further evidence is needed. The lung aeration and diaphragm changes achieved with these two strategies in healthy subjects have not been compared to date. METHODS: Twenty healthy subjects were recruited. Ten were ventilated with NIV and ten underwent HFNC. Lung impedance and diaphragmatic ultrasound measurements were performed before and after 30 min of respiratory support. The Mar-index was defined as the ratio of the diaphragm excursion-time index to the respiratory rate. RESULTS: Both groups showed significant decreases in respiratory rate (NIV: 14.4 (4.1) vs 10.4 (1.6), p = 0.009; HFNC: 13.6 (4.3) vs 7.9 (1.5) bpm, p = 0.002) and significant increases in the end-expiratory lung impedance (EELI) (NIV: 66,348(10,761) vs. 73,697 (6858), p = 0.005; HFNC: 66,252 (9793) vs 69,869 (9135), p = 0.012). NIV subjects showed a significant increase in non-dependent silent spaces (4.13 (2.25) vs 5.81 (1.49)%, p = 0.037) while the increase was more homogeneous with HFNC. The variation in EELI tended to be higher in NIV than in HFNC (8137.08 (6152.04) vs 3616.94 (3623.03), p = 0.077). The Mar-index was higher in HFNC group (13.15 vs 5.27 cm-sec2/bpm, p = 0.02). CONCLUSIONS: NIV and HFNC increased EELI in healthy subjects, suggesting an increase in the functional residual capacity. The EELI increase may be higher in NIV, but HFNC produced a more homogeneous change in lung ventilation. HFNC group has a higher MAR-index that could reflect a different ventilatory system adaptation.

Diaphragm Dysfunction in Mechanically Ventilated Patients. / Disfunción diafragmática: una realidad en el paciente ventilado mecánicamente.

Muscle involvement is found in most critical patients admitted to the intensive care unit (ICU). Diaphragmatic muscle alteration, initially included in this category, has been differentiated in recent years, and a specific type of muscular dysfunction has been shown to occur in patients undergoing mechanical ventilation. We found this muscle dysfunction to appear in this subgroup of patients shortly after the start of mechanical ventilation, observing it to be mainly associated with certain control modes, and also with sepsis and/or multi-organ failure. Although the specific etiology of process is unknown, the muscle presents oxidative stress and mitochondrial changes. These cause changes in protein turnover, resulting in atrophy and impaired contractility, and leading to impaired functionality. The term 'ventilator-induced diaphragm dysfunction' was first coined by Vassilakopoulos et al. in 2004, and this phenomenon, along with injury cause by over-distention of the lung and barotrauma, represents a challenge in the daily life of ventilated patients. Diaphragmatic dysfunction affects prognosis by delaying extubation, prolonging hospital stay, and impairing the quality of life of these patients in the years following hospital discharge. Ultrasound, a non-invasive technique that is readily available in most ICUs, could be used to diagnose this condition promptly, thus preventing delays in starting rehabilitation and positively influencing prognosis in these patients.

Prospective validation of right ventricular role in primary graft dysfunction after lung transplantation.

Primary graft dysfunction is a significant cause of lung transplant morbidity and mortality, but its underlying mechanisms are not completely understood. The aims of the present study were: 1) to confirm that right ventricular function is a risk factor for severe primary graft dysfunction; and 2) to propose a clinical model for predicting the development of severe primary graft dysfunction.A prospective cohort study was performed over 14 months. The primary outcome was development of primary graft dysfunction grade 3. An echocardiogram was performed immediately before transplantation, measuring conventional and speckle-tracking parameters. Pulmonary artery catheter data were also measured. A classification and regression tree was made to identify prognostic models for the development of severe graft dysfunction.70 lung transplant recipients were included. Patients who developed severe primary graft dysfunction had better right ventricular function, as estimated by cardiac index (3.5±0.8 versus 2.6±0.7 L·min-1·m-2, p<0.01) and basal longitudinal strain (-25.7±7.3% versus -19.5±6.6%, p<0.01). Regression tree analysis provided an algorithm based on the combined use of three variables (basal longitudinal strain, pulmonary fibrosis disease and ischaemia time), allowing accurate preoperative discrimination of three distinct subgroups with low (11-20%), intermediate (54%) and high (75%) risk of severe primary graft dysfunction (area under the receiver operating characteristic curve 0.81).Better right ventricular function is a risk factor for the development of severe primary graft dysfunction. Preoperative estimation of right ventricular function could allow early identification of recipients at increased risk, who would benefit the most from careful perioperative management in order to limit pulmonary overflow.

Influence of right ventricular function on the development of primary graft dysfunction after lung transplantation.

BACKGROUND: Primary graft dysfunction (PGD) remains a significant cause of lung transplant postoperative morbidity and mortality. The underlying mechanisms of PGD development are not completely understood. This study analyzed the effect of right ventricular function (RVF) on PGD development. METHODS: A retrospective analysis of a prospectively assessed cohort was performed at a single institution between July 2010 and June 2013. The primary outcome was development of PGD grade 3 (PGD3). Conventional echocardiographic parameters and speckle-tracking echocardiography, performed during the pre-transplant evaluation phase up to 1 year before surgery, were used to assess preoperative RVF. RESULTS: Included were 120 lung transplant recipients (LTr). Systolic pulmonary arterial pressure (48 ± 20 vs 41 ± 18 mm Hg; p = 0.048) and ischemia time (349 ± 73 vs 306 ± 92 minutes; p < 0.01) were higher in LTr who developed PGD3. Patients who developed PGD3 had better RVF estimated by basal free wall longitudinal strain (BLS; -24% ± 9% vs -20% ± 6%; p = 0.039) but had a longer intensive care unit length of stay and mechanical ventilation and higher 6-month mortality. BLS ≥ -21.5% was the cutoff that best identified patients developing PGD3 (area under the receiver operating characteristic curve, 0.70; 95% confidence interval, 0.54-0.85; p = 0.020). In the multivariate analysis, a BLS ≥ -21.5% was an independent risk factor for PGD3 development (odds ratio, 4.56; 95% confidence interval, 1.20-17.38; p = 0.026), even after adjusting for potential confounding. CONCLUSIONS: A better RVF, as measured by BLS, is a risk factor for severe PGD. Careful preoperative RVF assessment using speckle-tracking echocardiography may identify LTrs with the highest risk of developing PGD.

Patients with New York Heart Association class III heart failure may benefit with high flow nasal cannula supportive therapy: high flow nasal cannula in heart failure.

PURPOSE: High flow nasal cannula (HFNC) may decrease preload being associated with beneficial hemodynamic and respiratory effects in adults with heart failure. METHODS: This is a sequential intervention prospective study including 10 adults with New York Heart Association (NYHA) class III and left ventricle ejection fraction 45% or less. High flow gas was administered (fraction of inspired oxygen, 0.21) through nasal cannula (Optiflow(TM); Fisher & Paykel, Auckland, New Zealand). Sequential echocardiographies were performed at baseline, using HFNC with 20 lpm and 40 lpm and post-HFNC. A reduction greater than 20% in the estimated inspiratory collapse of the inferior vena cava (IVC) from baseline was considered clinically significant. RESULTS: Ten patients were included, with median age of 57 (44-65) years; 6 (60%) were female, and 8 (80%) had dilated cardiomyopathy. Median IVC inspiratory significantly (P<.05) decreased from baseline (37%) to HFNC with 20 lpm (28%) and HFNC with 40 lpm (21%), representing mean attributable reductions of 20% (95% confidence interval, 6-55) and 53% (95% confidence interval, 36-67) from baseline. Changes in the IVC inspiratory collapse were reversible after HFNC withdrawal. Respiratory rate was significantly reduced from 23 breaths per minute at baseline to 17 breaths per minute at HFNC with 20 lpm and 13 breaths per minute at HFNC with 40 lpm. In contrast, no significant changes in other echocardiographic or clinical variables were documented. CONCLUSION: These findings suggest that patients with NYHA class III heart failure may benefit with HFNC supportive therapy.