Comparison of limited driving pressure ventilation and low tidal volume strategies in adults with acute respiratory failure on mechanical ventilation: a randomized controlled trial.

BACKGROUND: Ventilator-induced lung injury (VILI) presents a grave risk to acute respiratory failure patients undergoing mechanical ventilation. Low tidal volume (LTV) ventilation has been advocated as a protective strategy against VILI. However, the effectiveness of limited driving pressure (plateau pressure minus positive end-expiratory pressure) remains unclear. OBJECTIVES: This study evaluated the efficacy of LTV against limited driving pressure in preventing VILI in adults with respiratory failure. DESIGN: A single-centre, prospective, open-labelled, randomized controlled trial. METHODS: This study was executed in medical intensive care units at Siriraj Hospital, Mahidol University, Bangkok, Thailand. We enrolled acute respiratory failure patients undergoing intubation and mechanical ventilation. They were randomized in a 1:1 allocation to limited driving pressure (LDP; ⩽15 cmH2O) or LTV (⩽8 mL/kg of predicted body weight). The primary outcome was the acute lung injury (ALI) score 7 days post-enrolment. RESULTS: From July 2019 to December 2020, 126 patients participated, with 63 each in the LDP and LTV groups. The cohorts had the mean (standard deviation) ages of 60.5 (17.6) and 60.9 (17.9) years, respectively, and they exhibited comparable baseline characteristics. The primary reasons for intubation were acute hypoxic respiratory failure (LDP 49.2%, LTV 63.5%) and shock-related respiratory failure (LDP 39.7%, LTV 30.2%). No significant difference emerged in the primary outcome: the median (interquartile range) ALI scores for LDP and LTV were 1.75 (1.00-2.67) and 1.75 (1.25-2.25), respectively (p = 0.713). Twenty-eight-day mortality rates were comparable: LDP 34.9% (22/63), LTV 31.7% (20/63), relative risk (RR) 1.08, 95% confidence interval (CI) 0.74-1.57, p = 0.705. Incidences of newly developed acute respiratory distress syndrome also aligned: LDP 14.3% (9/63), LTV 20.6% (13/63), RR 0.81, 95% CI 0.55-1.22, p = 0.348. CONCLUSIONS: In adults with acute respiratory failure, the efficacy of LDP and LTV in averting lung injury 7 days post-mechanical ventilation was indistinguishable. CLINICAL TRIAL REGISTRATION: The study was registered with the ClinicalTrials.gov database (identification number NCT04035915).

Limited breathing pressure or low amount of air given to the lung; which one is better for adults who need breathing help by ventilator machineWe conducted this research at Siriraj Hospital in Bangkok, Thailand, aiming to compare two ways of helping patients with breathing problems. We studied 126 patients who were randomly put into two groups. One group received a method where the pressure during breathing was limited (limited driving pressure: LDP), and the other group got a method where the amount of air given to the lungs was kept low (low tidal volume: LTV). We checked how bad the lung injury was at seven days later. The results showed that there was no difference between the two methods. Both ways of helping patients breathe had similar outcomes, and neither was significantly better than the other in preventing lung problems. The study suggests that both approaches work about the same for patients who need help with breathing using a machine.

Diaphragm weakness in late-onset Pompe disease: A complex interplay between lower motor neuron and muscle fibre degeneration.

BACKGROUND: Late-onset Pompe disease (LOPD) patients may still need ventilation support at some point of their disease course, despite regular recombinant human alglucosidase alfa treatment. This suggest that other pathophysiological mechanisms than muscle fibre lesion can contribute to the respiratory failure process. We investigate through neurophysiology whether spinal phrenic motor neuron dysfunction could contribute to diaphragm weakness in LOPD patients. MATERIAL AND METHODS: A group of symptomatic LOPD patients were prospectively studied in our centre from January 2022 to April 2023. We collected both demographic and clinical data, as well as neurophysiological parameters. Phrenic nerve conduction studies and needle EMG sampling of the diaphragm were perfomed. RESULTS: Eight treated LOPD patients (3 males, 37.5%) were investigated. Three patients (37.5%) with no respiratory involvement had normal phrenic nerve motor responses [median phrenic compound muscle action potential (CMAP) amplitude of 0.49 mV; 1st-3rd interquartile range (IQR), 0.48-0.65]. Those with respiratory failure (under nocturnal non-invasive ventilation) had abnormal phrenic nerve motor responses (median phrenic CMAP amplitude of 0 mV; 1st-3rd IQR, 0-0.15), and were then investigated with EMG. Diaphragm needle EMG revealed both myopathic and neurogenic changes in 3 (60%) and myopathic potentials in 1 patient. In the last one, no motor unit potentials could be recruited. CONCLUSIONS: Our study provide new insights regarding respiratory mechanisms in LOPD, suggesting a contribution of spinal phrenic motor neuron dysfunction for diaphragm weakness. If confirmed in further studies, our results recommend the need of new drugs crossing the blood-brain barrier.

Comparison of Different Tidal Volumes for Ventilation in Patients with an Acute Traumatic Cervical Spine Injury.

Background: There is scant literature comparing high tidal volume ventilation (HTV) over low tidal volume (LTV) ventilation in acute traumatic cervical spinal cord injury (CSCI). Objective: The aim of this prospective randomized controlled parallel-group, single-blinded study was to compare the effect of two different tidal volumes (12-15 mL/kg and 6-8 mL/kg) in CSCI on days to achieve ventilator-free breathing (VFB), PaO2/FIO2 ratio, the incidence of complications, requirement of vasopressor drugs, total duration of hospital stay, and mortality. Materials and Methods: We enrolled patients with acute high traumatic CSCI admitted to the neurotrauma intensive care unit within 24 h of injury, requiring mechanical ventilation. Participants were randomized to receive either HTV, 12-15 mL/kg (group H) or LTV, 6-8 mL/kg (group L) tidal volume ventilation. Results and Conclusions: A total of 56 patients, 28 in each group were analyzed. Patient demographics and injury severity were comparable between the groups. VFB was achieved in 23 and 19 patients in groups H and L, respectively. The median number of days required to achieve VFB was 3 (2, 56) and 8 (2, 50) days, P = 0.33; PaO2: FIO2 ratio was 364.0 ± 64 and 321.0 ± 67.0, P = 0.01; the incidence of atelectasis was 25% and 46%, P = 0.16, respectively, in group H and group L. The hemodynamic parameters and the vasopressor requirement were comparable in both groups. There was no barotrauma. The duration of hospital stay (P = 0.2) and mortality (P = 0.2) was comparable in both groups. There was no significant difference in days to achieve ventilator-free breathing with HTV (12-15 mL/kg) ventilation compared to LTV (6-8 mL/kg) ventilation in acute CSCI. The PaO2:FiO2 ratio was higher with the use of 12-15 mL/kg. No difference in mortality and duration of hospital stay was seen in either group.

Identification of factors impairing exercise capacity after severe COVID-19 pulmonary infection: a 3-month follow-up of prospective COVulnerability cohort.

BACKGROUND: Patient hospitalized for coronavirus disease 2019 (COVID-19) pulmonary infection can have sequelae such as impaired exercise capacity. We aimed to determine the frequency of long-term exercise capacity limitation in survivors of severe COVID-19 pulmonary infection and the factors associated with this limitation. METHODS: Patients with severe COVID-19 pulmonary infection were enrolled 3 months after hospital discharge in COVulnerability, a prospective cohort. They underwent cardiopulmonary exercise testing, pulmonary function test, echocardiography, and skeletal muscle mass evaluation. RESULTS: Among 105 patients included, 35% had a reduced exercise capacity (VO2peak < 80% of predicted). Compared to patients with a normal exercise capacity, patients with reduced exercise capacity were more often men (89.2% vs. 67.6%, p = 0.015), with diabetes (45.9% vs. 17.6%, p = 0.002) and renal dysfunction (21.6% vs. 17.6%, p = 0.006), but did not differ in terms of initial acute disease severity. An altered exercise capacity was associated with an impaired respiratory function as assessed by a decrease in forced vital capacity (p < 0.0001), FEV1 (p < 0.0001), total lung capacity (p < 0.0001) and DLCO (p = 0.015). Moreover, we uncovered a decrease of muscular mass index and grip test in the reduced exercise capacity group (p = 0.001 and p = 0.047 respectively), whilst 38.9% of patients with low exercise capacity had a sarcopenia, compared to 10.9% in those with normal exercise capacity (p = 0.001). Myocardial function was normal with similar systolic and diastolic parameters between groups whilst reduced exercise capacity was associated with a slightly shorter pulmonary acceleration time, despite no pulmonary hypertension. CONCLUSION: Three months after a severe COVID-19 pulmonary infection, more than one third of patients had an impairment of exercise capacity which was associated with a reduced pulmonary function, a reduced skeletal muscle mass and function but without any significant impairment in cardiac function.

Potential for the lung recruitment and the risk of lung overdistension during 21 days of mechanical ventilation in patients with COVID-19 after noninvasive ventilation failure: the COVID-VENT observational trial.

BACKGROUND: Data on the lung respiratory mechanics and gas exchange in the time course of COVID-19-associated respiratory failure is limited. This study aimed to explore respiratory mechanics and gas exchange, the lung recruitability and risk of overdistension during the time course of mechanical ventilation. METHODS: This was a prospective observational study in critically ill mechanically ventilated patients (n = 116) with COVID-19 admitted into Intensive Care Units of Sechenov University. The primary endpoints were: «optimum¼ positive end-expiratory pressure (PEEP) level balanced between the lowest driving pressure and the highest SpO2 and number of patients with recruitable lung on Days 1 and 7 of mechanical ventilation. We measured driving pressure at different levels of PEEP (14, 12, 10 and 8 cmH2O) with preset tidal volume, and with the increase of tidal volume by 100 ml and 200 ml at preset PEEP level, and calculated static respiratory system compliance (CRS), PaO2/FiO2, alveolar dead space and ventilatory ratio on Days 1, 3, 5, 7, 10, 14 and 21. RESULTS: The «optimum¼ PEEP levels on Day 1 were 11.0 (10.0-12.8) cmH2O and 10.0 (9.0-12.0) cmH2O on Day 7. Positive response to recruitment was observed on Day 1 in 27.6% and on Day 7 in 9.2% of patients. PEEP increase from 10 to 14 cmH2O and VT increase by 100 and 200 ml led to a significant decrease in CRS from Day 1 to Day 14 (p < 0.05). Ventilatory ratio was 2.2 (1.7-2,7) in non-survivors and in 1.9 (1.6-2.6) survivors on Day 1 and decreased on Day 7 in survivors only (p < 0.01). PaO2/FiO2 was 105.5 (76.2-141.7) mmHg in non-survivors on Day 1 and 136.6 (106.7-160.8) in survivors (p = 0.002). In survivors, PaO2/FiO2 rose on Day 3 (p = 0.008) and then between Days 7 and 10 (p = 0.046). CONCLUSION: Lung recruitability was low in COVID-19 and decreased during the course of the disease, but lung overdistension occurred at «intermediate¼ PEEP and VT levels. In survivors gas exchange improvements after Day 7 mismatched CRS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04445961 . Registered 24 June 2020-Retrospectively registered.

Pulmonary Artery Catheter in Patients with Severe Acute Pancreatitis: A Single-Center Retrospective Study.

OBJECTIVE: It is still uncertain what effects pulmonary artery catheter (PAC)-guided resuscitation has on outcomes for patients with severe acute pancreatitis (SAP). Therefore, we aimed to investigate the effect of PAC on hospital mortality in patients with SAP. METHODS: We collected the data of patients with a diagnosis of SAP from January 10, 2017, to July 30, 2019. Patients were divided into a PAC group and a control group. The primary outcome measured was the day-28 mortality. Secondary outcomes included day-90 mortality, duration of ICU and hospital stay, ventilation days, usage of renal support and vasoactive agents, incidences of acute abdominal compartment syndrome, infusion volumes, and fluid balance and hemodynamic characteristics measured by the PAC. Kaplan-Meier analysis was applied to estimate survival outcomes. Complications related to PAC were also analyzed. RESULTS: There was no significant difference between the PAC group and the control group for day-28 mortality (22.7% vs. 30%, odds ratio, 0.69; 95% CI 0.31-1.52; P = 0.35). The duration of ICU stay in the PAC group was shorter (P = 0.00), and the rate of dependence on renal support treatment was lower in the PAC group than in the control group (P = 0.03). There was no difference in other secondary outcomes and no significant difference in the survival curve between the two groups (log-rank P = 0.72, X2 = 0.13). However, SAP patients inserted PAC within 24 h ICU admission showed that duration of renal support therapy in PAC patients within 24 h ICU admission (mean days, 1.60; standard deviation, 0.14) was shorter than those with 24-72 h ICU admission (mean days, 2.94; standard deviation, 0.73; P = 0.03). The organ failure rates (1 organ, 2 organs and 3 organs) were all lower in PAC patients within 24 h ICU admission than with 24-72 h ICU admission (P = 0.02, P = 0.02, P = 0.048, respectively). CONCLUSION: In patients with severe acute pancreatitis, PAC-guided fluid resuscitation shortened the duration of ICU stay, and patients in the PAC group had a lower rate of dependence on renal support, while no benefit in terms of mortality was observed. However, SAP patients inserted PAC within 24 h ICU admission showed shorter duration of renal support therapy and lower organ failure rates than those with 24-72 h ICU admission, indicating that early use of PAC, especially within 24 h, might be better for SAP patients.

National Temporal Trends in Hospitalization and Inpatient Mortality in Patients With Pulmonary Sarcoidosis in the United States Between 2007 and 2018.

BACKGROUND: Sarcoidosis-related hospitalizations have been increasing in the past decade. There is a paucity of data on mortality trends over time in patients with pulmonary sarcoidosis and respiratory failure who are hospitalized. RESEARCH QUESTION: What are the national temporal trends over time in hospitalization and inpatient mortality rates in patients with pulmonary sarcoidosis and respiratory failure hospitalized in the United States between 2007 and 2018? STUDY DESIGN AND METHODS: Hospitalization data between 2007 and 2018 were extracted from the National Inpatient Sample for subjects with pulmonary sarcoidosis. Inpatient mortality was stratified by age, respiratory failure, mechanical ventilation (MV), hospital location, and setting (rural vs urban, academic vs nonacademic). A Cochran-Armitage test for trend was used to assess the linear trend in mortality, respiratory failure, and need for MV. RESULTS: Hospitalizations in patients with pulmonary sarcoidosis increased from 258.5 per 1,000,000 hospitalizations in 2007 to 705.7 per 1,000,000 in 2018. Hospitalizations for respiratory failure increased ninefold from 25.9 to 239.4 per 1,000,000 hospitalizations, and the need for MV increased threefold from 9.4 per 1,000,000 in 2007 to 29.4 per 1,000,000 in 2018. All-cause inpatient mortality was 2.6%; however, mortality was 13 times higher in patients with respiratory failure (10.6% vs 0.8%) and 26 times higher in patients who required MV (31.2% vs 1.2%). Inpatient mortality associated with respiratory failure declined 50% from 17.2% in 2007 to 6.6% in 2018. Independent inpatient mortality predictors were older age (adjusted hazard ratio [aHR], 1.025), respiratory failure (aHR, 3.12), need for MV (aHR, 6.01), pulmonary hypertension (pHTN; aHR, 1.44), pulmonary embolism (aHR, 1.61), and frailty (aHR, 3.10). INTERPRETATION: Hospitalizations for respiratory failure in patients with pulmonary sarcoidosis are increasing; however, inpatient mortality from respiratory failure has declined. Older age, respiratory failure, pHTN, and frailty are important predictors of inpatient mortality in patients with pulmonary sarcoidosis who are hospitalized.

Severity of respiratory failure and computed chest tomography in acute COVID-19 correlates with pulmonary function and respiratory symptoms after infection with SARS-CoV-2: An observational longitudinal study over 12 months.

INTRODUCTION: Prospective and longitudinal data on pulmonary injury over one year after acute coronavirus disease 2019 (COVID-19) are sparse. We aim to determine reductions in pulmonary function and respiratory related quality of life up to 12 months after acute COVID-19. METHODS: Patients with acute COVID-19 were enrolled into an ongoing single-centre, prospective observational study and prospectively examined 6 weeks, 3, 6 and 12 months after onset of COVID-19 symptoms. Chest CT-scans, pulmonary function and symptoms assessed by St. Georges Respiratory Questionnaire were used to evaluate respiratory limitations. Patients were stratified according to severity of acute COVID-19. RESULTS: Median age of all patients was 57 years, 37.8% were female. Higher age, male sex and higher BMI were associated with acute-COVID-19 severity (p < 0.0001, 0.001 and 0.004 respectively). Also, pulmonary restriction and reduced carbon monoxide diffusion capacity was associated with disease severity. In patients with restriction and impaired diffusion capacity, FVC improved over 12 months from 61.32 to 71.82, TLC from 68.92 to 76.95, DLCO from 60.18 to 68.98 and KCO from 81.28 to 87.80 (percent predicted values; p = 0.002, 0.045, 0.0002 and 0.0005). The CT-score of lung involvement in the acute phase was associated with restriction and reduction in diffusion capacity in follow-up. Respiratory symptoms improved for patients in higher severity groups during follow-up, but not for patients with initially mild disease. CONCLUSION: Severity of respiratory failure during COVID-19 correlates with the degree of pulmonary function impairment and respiratory quality of life in the year after acute infection.

Lower versus higher oxygenation targets in critically ill patients with severe hypoxaemia: secondary Bayesian analysis to explore heterogeneous treatment effects in the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial.

BACKGROUND: In the Handling Oxygenation Targets in the Intensive Care Unit (HOT-ICU) trial, a lower (8 kPa) vs a higher (12 kPa) PaO2 target did not affect mortality amongst critically ill adult patients. We used Bayesian statistics to evaluate any heterogeneity in the effect of oxygenation targets on mortality between different patient groups within the HOT-ICU trial. METHODS: We analysed 90-day all-cause mortality using adjusted Bayesian logistic regression models, and assessed heterogeneous treatment effects according to four selected baseline variables using both hierarchical models of subgroups and models with interactions on the continuous scales. Results are presented as mortality probability (%) and relative risk (RR) with 95% credibility intervals (CrI). RESULTS: All 2888 patients in the intention-to-treat cohort of the HOT-ICU trial were included. The adjusted 90-day mortality rates were 43.0% (CrI: 38.3-47.8%) and 42.3% (CrI: 37.7-47.1%) in the lower and higher oxygenation groups, respectively (RR 1.02 [CrI: 0.93-1.11]), with 36.5% probability of an RR <1.00. Analyses of heterogeneous treatment effects suggested a dose-response relationship between baseline norepinephrine dose and increased mortality with the lower oxygenation target, with 95% probability of increased mortality associated with the lower oxygenation target as norepinephrine doses increased. CONCLUSIONS: A lower oxygenation target was unlikely to affect overall mortality amongst critically ill adult patients with acute hypoxaemic respiratory failure. However, our results suggest an increasing mortality risk for patients with a lower oxygen target as the baseline norepinephrine dose increases. These findings warrant additional investigation. CLINICAL TRIAL REGISTRATION: NCT03174002.

Reduced pulmonary functions and respiratory muscle strength in Type 2 diabetes mellitus and its association with glycemic control.

OBJECTIVE: Diabetes mellitus is one of the main devastating causes of mortality and morbidity due to its detrimental complications. We aimed to evaluate the pulmonary functions and respiratory muscle strength in relationship with glycemic control and gender in type 2 Diabetes Mellitus (T2DM). MATERIALS AND METHODS: This cross-sectional study was performed at King Saud University and King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia from June 2107 to June 2019. We evaluated pulmonary functions, respiratory muscle strength, body composition and glycemic control in T2DM (n=110) and control group (n=119). Gender differences were also evaluated in T2DM. RESULTS: Subjects with T2DM have significantly decreased forced vital capacity (FVC) (3.6±0.7 vs 3.3±0.9, p = 0.012), forced expiratory volume in first second (FEV1) (3.3±2.2 vs 2.7±0.6, p = 0.019), peak expiratory flow (PEF) (127.4±210.9 vs. 49.2±133.6, p = 0.003), FEF25-75 (3.6±1.3 vs. 3.1±1.1, p-value = 0.025), and maximum inspiratory pressure (MIP) (99.3±26.9 vs. 87.4±19.3, p=0.001). However, no significant difference between control and diabetes was found in maximum expiratory pressure (MEP) (132.5±34.9 vs 126.2±30.0, p = 0.202). Significant reduction in FVC (male=3.7±0.8 vs female = 3.0±0.7 p = 0.000), FEV1 (3.3±1.9 vs 2.6±0.5 p = 0.000), FEF25-75 (3.6 ± 1.3 vs 2.9 ± 1.0 with p-value = 0.000), MIP (96.9±23.1 vs 87.5±27.1 with p = 0.017), and MEP (134.0±32.2 vs. 120.1±33.5 with p = .011) were observed in females compared to males in T2DM subjects. CONCLUSIONS: Decline in the pulmonary function and inspiratory muscle strength are associated with poor glycemic control in T2DM. Moreover, there are significant differences between male and female in lung parameters and inspiratory as well as expiratory muscles strength. The exact pathophysiological mechanism to explain this association requires further investigations.

Cardiogenic shock with highly complicated course after influenza A virus infection treated with vva-ECMO and Impella CP (ECMELLA): a case report.

BACKGROUND: The value of mechanical circulatory support (MCS) in cardiogenic shock, especially the combination of the ECMELLA approach (Impella combined with ECMO), remains controversial. CASE PRESENTATION: A previously healthy 33-year-old female patient was submitted to a local emergency department with a flu-like infection and febrile temperatures up to 39 °C. The patient was tested positive for type-A influenza, however negative for SARS-CoV-2. Despite escalated invasive ventilation, refractory hypercapnia (paCO2: 22 kPa) with severe respiratory acidosis (pH: 6.9) and a rising norepinephrine rate occurred within a few hours. Due to a Horovitz-Index < 100, out-of-centre veno-venous extracorporeal membrane oxygenation (vv-ECMO)-implantation was performed. A CT-scan done because of anisocoria revealed an extended dissection of the right vertebral artery. While the initial left ventricular function was normal, echocardiography revealed severe global hypokinesia. After angiographic exclusion of coronary artery stenoses, we geared up LV unloading by additional implantation of an Impella CP and expanded the vv-ECMO to a veno-venous-arterial ECMO (vva-ECMO). Clinically relevant bleeding from the punctured femoral arteries resulted in massive transfusion and was treated by vascular surgery later on. Under continued MCS, LVEF increased to approximately 40% 2 days after the initiation of ECMELLA. After weaning, the Impella CP was explanted at day 5 and the vva-ECMO was removed on day 9, respectively. The patient was discharged in an unaffected neurological condition to rehabilitation 25 days after the initial admission. CONCLUSIONS: This exceptional case exemplifies the importance of aggressive MCS in severe cardiogenic shock, which may be especially promising in younger patients with non-ischaemic cardiomyopathy and potentially reversible causes of cardiogenic shock. This case impressively demonstrates that especially young patients may achieve complete neurological restoration, even though the initial prognosis may appear unfavourable.

Ventilatory responses during and following hypercapnic gas challenge are impaired in male but not female endothelial NOS knock-out mice.

The roles of endothelial nitric oxide synthase (eNOS) in the ventilatory responses during and after a hypercapnic gas challenge (HCC, 5% CO2, 21% O2, 74% N2) were assessed in freely-moving female and male wild-type (WT) C57BL6 mice and eNOS knock-out (eNOS-/-) mice of C57BL6 background using whole body plethysmography. HCC elicited an array of ventilatory responses that were similar in male and female WT mice, such as increases in breathing frequency (with falls in inspiratory and expiratory times), and increases in tidal volume, minute ventilation, peak inspiratory and expiratory flows, and inspiratory and expiratory drives. eNOS-/- male mice had smaller increases in minute ventilation, peak inspiratory flow and inspiratory drive, and smaller decreases in inspiratory time than WT males. Ventilatory responses in female eNOS-/- mice were similar to those in female WT mice. The ventilatory excitatory phase upon return to room-air was similar in both male and female WT mice. However, the post-HCC increases in frequency of breathing (with decreases in inspiratory times), and increases in tidal volume, minute ventilation, inspiratory drive (i.e., tidal volume/inspiratory time) and expiratory drive (i.e., tidal volume/expiratory time), and peak inspiratory and expiratory flows in male eNOS-/- mice were smaller than in male WT mice. In contrast, the post-HCC responses in female eNOS-/- mice were equal to those of the female WT mice. These findings provide the first evidence that the loss of eNOS affects the ventilatory responses during and after HCC in male C57BL6 mice, whereas female C57BL6 mice can compensate for the loss of eNOS, at least in respect to triggering ventilatory responses to HCC.

Respiratory Drive in Patients with Sepsis and Septic Shock: Modulation by High-flow Nasal Cannula.

BACKGROUND: Experimental and pilot clinical data suggest that spontaneously breathing patients with sepsis and septic shock may present increased respiratory drive and effort, even in the absence of pulmonary infection. The study hypothesis was that respiratory drive and effort may be increased in septic patients and correlated with extrapulmonary determinant and that high-flow nasal cannula may modulate drive and effort. METHODS: Twenty-five nonintubated patients with extrapulmonary sepsis or septic shock were enrolled. Each patient underwent three consecutive steps: low-flow oxygen at baseline, high-flow nasal cannula, and then low-flow oxygen again. Arterial blood gases, esophageal pressure, and electrical impedance tomography data were recorded toward the end of each step. Respiratory effort was measured as the negative swing of esophageal pressure (ΔPes); drive was quantified as the change in esophageal pressure during the first 500 ms from start of inspiration (P0.5). Dynamic lung compliance was calculated as the tidal volume measured by electrical impedance tomography, divided by ΔPes. The results are presented as medians [25th to 75th percentile]. RESULTS: Thirteen patients (52%) were in septic shock. The Sequential Organ Failure Assessment score was 5 [4 to 9]. During low-flow oxygen at baseline, respiratory drive and effort were elevated and significantly correlated with arterial lactate (r = 0.46, P = 0.034) and inversely with dynamic lung compliance (r = -0.735, P < 0.001). Noninvasive support by high-flow nasal cannula induced a significant decrease of respiratory drive (P0.5: 6.0 [4.4 to 9.0] vs. 4.3 [3.5 to 6.6] vs. 6.6 [4.9 to 10.7] cm H2O, P < 0.001) and effort (ΔPes: 8.0 [6.0 to 11.5] vs. 5.5 [4.5 to 8.0] vs. 7.5 [6.0 to 12.6] cm H2O, P < 0.001). Oxygenation and arterial carbon dioxide levels remained stable during all study phases. CONCLUSIONS: Patients with sepsis and septic shock of extrapulmonary origin present elevated respiratory drive and effort, which can be effectively reduced by high-flow nasal cannula.

A Rare Cause of Respiratory Insufficiency in a 30-Year-Old Transgender Woman.

CASE PRESENTATION: A 30-year-old transgender woman who was HIV positive presented to the ED with progressive severe dyspnea and hemoptysis that started 1 day earlier. The patient was undergoing antiretroviral therapy with emtricitabine-rilpivirine-tenofovir with good compliance and feminizing hormone therapy with cyproterone acetate. She was otherwise healthy and was not taking any other medications.

Pathophysiology of respiratory failure in patients with osteogenesis imperfecta: a systematic review.

INTRODUCTION: Respiratory failure is a major cause of death in patients with Osteogenesis Imperfecta. Moreover, respiratory symptoms seem to have a dramatic impact on their quality of life. It has long been thought that lung function disorders in OI are mainly due to changes in the thoracic wall, caused by bone deformities. However, recent studies indicate that alterations in the lung itself can also undermine respiratory health. OBJECTIVES: Is there any intrapulmonary alteration in Osteogenesis Imperfecta that can explain decreased pulmonary function? The aim of this systematic literature review is to investigate to what extent intrapulmonary or extrapulmonary thoracic changes contribute to respiratory dysfunction in Osteogenesis Imperfecta. METHODS: A literature search (in PubMed, Embase, Web of Science, and Cochrane), which included articles from inception to December 2020, was performed in accordance with the PRISMA guidelines. RESULTS: Pulmonary function disorders have been described in many studies as secondary to scoliosis or to thoracic skeletal deformities. The findings of this systematic review suggest that reduced pulmonary function can also be caused by a primary pulmonary problem due to intrinsic collagen alterations. CONCLUSIONS: Based on the most recent studies, the review indicates that pulmonary defects may be a consequence of abnormal collagen type I distorting the intrapulmonary structure of the lung. Lung function deteriorates further when intrapulmonary defects are combined with severe thoracic abnormalities. This systematic review reveals novel findings of the underlying pathological mechanism which have clinical and diagnostic implications for the assessment and treatment of pulmonary function disorders in Osteogenesis Imperfecta.KEY MESSAGESDecreased pulmonary function in Osteogenesis Imperfecta can be attributed to primary pulmonary defects due to intrapulmonary collagen alterations and not solely to secondary problems arising from thoracic skeletal dysplasia.Type I collagen defects play a crucial role in the development of the lung parenchyma and defects, therefore, affect pulmonary function. More awareness is needed among physicians about pulmonary complications in Osteogenesis Imperfecta to develop novel concepts on clinical and diagnostic assessment of pulmonary functional disorders.

Development and Validation of Diagnostic Models for Hand-Foot-and-Mouth Disease in Children.

OBJECTIVE: To find risk markers and develop new clinical predictive models for the differential diagnosis of hand-foot-and-mouth disease (HFMD) with varying degrees of disease. METHODS: 19766 children with HFMD and 64 clinical indexes were included in this study. The patients included in this study were divided into the mild patients' group (mild) with 12292 cases, severe patients' group (severe) with 6508 cases, and severe patients with respiratory failure group (severe-RF) with 966 cases. Single-factor analysis was carried out on 64 indexes collected from patients when they were admitted to the hospital, and the indexes with statistical differences were selected as the prediction factors. Binary multivariate logistic regression analysis was used to construct the prediction models and calculate the adjusted odds ratio (OR). RESULTS: SP, DP, NEUT#, NEUT%, RDW-SD, RDW-CV, GGT, CK/CK-MB, and Glu were risk markers in mild/severe, mild/severe-RF, and severe/severe-RF. Glu was a diagnostic marker for mild/severe-RF (AUROC = 0.80, 95% CI: 0.78-0.82); the predictive model constructed by temperature, SP, MOMO%, EO%, RDW-SD, GLB, CRP, Glu, BUN, and Cl could be used for the differential diagnosis of mild/severe (AUROC > 0.84); the predictive model constructed by SP, age, NEUT#, PCT, TBIL, GGT, Mb, ß2MG, Glu, and Ca could be used for the differential diagnosis of severe/severe-RF (AUROC > 0.76). CONCLUSION: By analyzing clinical indicators, we have found the risk markers of HFMD and established suitable predictive models.

Evaluation of G protein bias and ß-arrestin 2 signaling in opioid-induced respiratory depression.

Respiratory depression is a potentially fatal side effect of opioid analgesics and a major limitation to their use. G protein-biased opioid agonists have been proposed as "safer" analgesics with less respiratory depression. These agonists are biased to activate G proteins rather than ß-arrestin signaling. Respiratory depression has been shown to correlate with both G protein bias and intrinsic efficacy, and recent work has refuted the role of ß-arrestin signaling in opioid-induced respiratory depression. In addition, there is substantial evidence that G proteins do, in fact, mediate respiratory depression by actions in respiratory-controlling brainstem neurons. Based on these studies, we provide the perspective that protection from respiratory depression displayed by newly developed G protein-biased agonists is due to factors other than G protein versus arrestin bias.