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To characterize clusters of double triggering and ineffective inspiratory efforts throughout mechanical ventilation and investigate their associations with mortality and duration of ICU stay and mechanical ventilation.Registry-based, real-world study.Asynchronies during invasive mechanical ventilation can occur as isolated events or in clusters and might be related to clinical outcomes.Adults requiring mechanical ventilation greater than 24 hours for whom greater than or equal to 70% of ventilator waveforms were available.We identified clusters of double triggering and ineffective inspiratory efforts and determined their power and duration. We used Fine-Gray's competing risk model to analyze their effects on mortality and generalized linear models to analyze their effects on duration of mechanical ventilation and ICU stay.We analyzed 58,625,796 breaths from 180 patients. All patients had clusters (mean/d, 8.2 [5.4-10.6]; mean power, 54.5 [29.6-111.4]; mean duration, 20.3 min [12.2-34.9 min]). Clusters were less frequent during the first 48 hours (5.5 [2.5-10] vs 7.6 [4.4-9.9] in the remaining period [p = 0.027]). Total number of clusters/d was positively associated with the probability of being discharged alive considering the total period of mechanical ventilation (p = 0.001). Power and duration were similar in the two periods. Power was associated with the probability of being discharged dead (p = 0.03), longer mechanical ventilation (p0.001), and longer ICU stay (p = 0.035); cluster duration was associated with longer ICU stay (p = 0.027).Clusters of double triggering and ineffective inspiratory efforts are common. Although higher numbers of clusters might indicate better chances of survival, clusters with greater power and duration indicate a risk of worse clinical outcomes.

Nitric oxide (NO) is a biologically active molecule approved for the treatment of pulmonary hypertension in newborn patients. Commercially available NO delivery systems use pressurized cylinders as the source of NO and a sensor to control the concentrations of NO and nitrogen dioxide (NO2) delivered. Cylinder-based delivery systems are safe and widely used around the world, but they are bulky, expensive, and reliant on a robust supply chain. In the past few years, novel NO generators and delivery systems have been developed to overcome these limitations. Electric NO generators produce NO from ambient air using high-voltage electrical discharge to ionize air, which leads to the formation of NO, NO2, and ozone (O3). A scavenging system is incorporated to reduce the concentration of the toxic byproducts generated in this type of system. NO can also be generated by the reduction of NO2 by ascorbic acid or released from liquid solutions or solid nanoparticles. The development of easy-to-use, safe, and portable NO delivery systems may enable the delivery of NO in the out-patient setting or at home. Furthermore, non-cylinder-based NO generators reduce the cost of NO production and storage and may therefore make NO delivery feasible in low-resource settings. Here we review commercially available systems that can generate and administer inhalable NO.

Objectives To measure the impact of clusters of double triggering on clinical outcomes. Design Prospective cohort study. Setting Respiratory ICU in Brazil. Patients Adult patients under recent mechanical ventilation and with expectation of mechanical ventilation for more than 24 hours after enrollment. Interventions None. Measurements and main results We used a dedicated software to analyze ventilator waveforms throughout the entire period of mechanical ventilation and detect double triggering. We defined a cluster of double triggering as a period of time containing at least six double triggering events in a 3-minute period. Patients were followed until hospital discharge. We addressed the association between the presence and the duration of clusters with clinical outcomes. A total of 103 patients were enrolled in the study and 90 (87%) had at least one cluster of double triggering. The median number of clusters per patient was 19 (interquartile range, 6-41), with a median duration of 8 minutes (6-12 min). Compared with patients who had no clusters, patients with at least one cluster had longer duration of mechanical ventilation (7 d [4-11 d] vs 2 d [2-3 d]) and ICU length of stay (9 d [7-16 d] vs 13 d [2-8 d]). Thirty-three patients had high cumulative duration of clusters of double triggering (≥ 12 hr), and it was associated with longer duration of mechanical ventilation, fewer ventilator-free days, and longer ICU length of stay. Adjusted by duration of mechanical ventilation and severity of illness, high cumulative duration of clusters was associated with shorter survival at 28 days (hazard ratio, 2.09 d; 95% CI, 1.04-4.19 d). Conclusions Clusters of double triggering are common and were associated with worse clinical outcomes. Patients who had a high cumulative duration of clusters had fewer ventilator-free days, longer duration of mechanical ventilation, longer ICU length of stay, and shorter survival than patients with low cumulative duration of cluster.

Purpose of review Obesity prevalence is increasing in most countries in the world. In the United States, 42% of the population is obese (body mass index (BMI) > 30) and 9.2% is obese class III (BMI > 40). One of the greatest challenges in critically ill patients with obesity is the optimization of mechanical ventilation. The goal of this review is to describe respiratory physiologic changes in patients with obesity and discuss possible mechanical ventilation strategies to improve respiratory function. Recent findings Individualized mechanical ventilation based on respiratory physiology after a decremental positive end-expiratory pressure (PEEP) trial improves oxygenation and respiratory mechanics. In a recent study, mortality of patients with respiratory failure and obesity was reduced by about 50% when mechanical ventilation was associated with the use of esophageal manometry and electrical impedance tomography (EIT). Summary Obesity greatly alters the respiratory system mechanics causing atelectasis and prolonged duration of mechanical ventilation. At present, novel strategies to ventilate patients with obesity based on individual respiratory physiology showed to be superior to those based on standard universal tables of mechanical ventilation. Esophageal manometry and EIT are essential tools to systematically assess respiratory system mechanics, safely adjust relatively high levels of PEEP, and improve chances for successful weaning.

Rationale: Obesity is characterized by elevated pleural pressure (Ppl) and worsening atelectasis during mechanical ventilation in patients with acute respiratory distress syndrome (ARDS). Objectives: To determine the effects of a lung recruitment maneuver (LRM) in the presence of elevated Ppl on hemodynamics, left and right ventricular pressure, and pulmonary vascular resistance. We hypothesized that elevated Ppl protects the cardiovascular system against high airway pressure and prevents lung overdistension. Methods: First, an interventional crossover trial in adult subjects with ARDS and a body mass index ≥ 35 kg/m2 (n = 21) was performed to explore the hemodynamic consequences of the LRM. Second, cardiovascular function was studied during low and high positive end-expiratory pressure (PEEP) in a model of swine with ARDS and high Ppl (n = 9) versus healthy swine with normal Ppl (n = 6). Measurements and Main Results: Subjects with ARDS and obesity (body mass index = 57 ± 12 kg/m2) after LRM required an increase in PEEP of 8 (95% confidence interval [95% CI], 7–10) cm H2O above traditional ARDS Network settings to improve lung function, oxygenation and V./Q. matching, without impairment of hemodynamics or right heart function. ARDS swine with high Ppl demonstrated unchanged transmural left ventricular pressure and systemic blood pressure after the LRM protocol. Pulmonary arterial hypertension decreased (8 [95% CI, 13–4] mm Hg), as did vascular resistance (1.5 [95% CI, 2.2–0.9] Wood units) and transmural right ventricular pressure (10 [95% CI, 15–6] mm Hg) during exhalation. LRM and PEEP decreased pulmonary vascular resistance and normalized the V./Q. ratio. Conclusions: High airway pressure is required to recruit lung atelectasis in patients with ARDS and class III obesity but causes minimal overdistension. In addition, patients with ARDS and class III obesity hemodynamically tolerate LRM with high airway pressure. Clinical trial registered with www.clinicaltrials.gov (NCT 02503241).

Patients with obstructive sleep apnea (OSA) are at risk for adverse events when moderate sedation is administered by nurse protocols (NAMS) under the guidance of non-anesthesiologists. An algorithm was applied for the appropriate section of patients to receive NAMS and the application of continuous positive airway pressure (CPAP).An algorithm was developed for patients with OSA who were scheduled for gastroenterology, radiology, and cardiology procedures using NAMS. Those with normal airways and without contraindications for NAMS were classified as CPAP-independent (CPAP-I; not routinely used) or CPAP-dependent (CPAP-D; always used). CPAP machines were brought in by CPAP-D patients or supplied by the hospital and set at a patient's routine setting or 10 cm HSince the inception of this protocol in 2008, 803 patients with OSA safely underwent procedures using either personal CPAP or CPAP provided by the hospital.Patients with OSA can safely have NAMS for procedures when CPAP is applied based on a protocol that considers airway evaluation, the procedure, and whether there is dependence upon CPAP.

Purpose We hypothesized that neurally adjusted ventilatory assist (NAVA) compared to conventional lung-protective mechanical ventilation (MV) decreases duration of MV and mortality in patients with acute respiratory failure (ARF). Methods We carried out a multicenter, randomized, controlled trial in patients with ARF from several etiologies. Intubated patients ventilated for ≤ 5 days expected to require MV for ≥ 72 h and able to breathe spontaneously were eligible for enrollment. Eligible patients were randomly assigned based on balanced treatment assignments with a computerized randomization allocation sequence to two ventilatory strategies: (1) lung-protective MV (control group), and (2) lung-protective MV with NAVA (NAVA group). Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days (VFDs) at 28 days. Secondary outcome was all-cause hospital mortality. All analyses were done according to the intention-to-treat principle. Results Between March 2014 and October 2019, we enrolled 306 patients and randomly assigned 153 patients to the NAVA group and 153 to the control group. Median VFDs were higher in the NAVA than in the control group (22 vs. 18 days; between-group difference 4 days; 95% confidence interval [CI] 0 to 8 days; p = 0.016). At hospital discharge, 39 (25.5%) patients in the NAVA group and 47 (30.7%) patients in the control group had died (between-group difference − 5.2%, 95% CI − 15.2 to 4.8, p = 0.31). Other clinical, physiological or safety outcomes did not differ significantly between the trial groups. Conclusion NAVA decreased duration of MV although it did not improve survival in ventilated patients with ARF. Electronic supplementary material The online version of this article (10.1007/s00134-020-06181-5) contains supplementary material, which is available to authorized users.

High-dose nitric oxide is a novel treatment associated with improved oxygenation and decreased tachypnea in pregnant patients with severe coronavirus disease 2019 (COVID-19)., BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160–200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160–200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.

BACKGROUND: Bronchiolitis is the most common cause of admission in children < 2 y of age in the United States. The standard of care involves supportive measures, including noninvasive interventions such as CPAP. CPAP is traditionally delivered through a full face mask; however, pediatric ICUs have been exploring the use of the RAM cannula by Neotech as a mode of CPAP delivery. The level of CPAP delivered via the RAM cannula is uncertain. We performed an in vitro study to determine the level of CPAP delivered via the RAM cannula utilizing a pediatric lung model. METHODS: Models of 7 sizes of pediatric upper airways, produced with a 3-dimensional printer, were connected to a breathing simulator. We applied each size of RAM cannula to weight-appropriate airway and lung compliance parameters, delivering pressures of 5, 7, and 10 cm H(2)O using a ventilator in the CPAP mode. Leaks of 0%, 20%, 40%, and 60% were generated to emulate a complete seal, a poor fit, and open-mouth breathing. The outcome measure was the difference in CPAP, referred to as “%leak effect,” measured by the lung simulator relative to the CPAP set on the ventilator. RESULTS: We found that set CPAP of 5–10 cm H(2)O generated measured CPAP ranging from 2.6 to 9.7 cm H(2)O. For the set CPAP levels of 5, 7, and 10 cm H(2)O, the mean %leak effect values of measured CPAP from the set CPAP were –25%, –26%, and –25.7%, respectively. For each specific cannula-airway combination, increasing the set pressure and decreasing the air leak resulted in higher levels of CPAP delivered. CONCLUSIONS: The RAM cannula delivered varying amounts of CPAP, with a percent loss of approximately –25% depending on the level of leak in the system. With minimal leak, it is conceivable that the RAM cannula can be used to deliver clinically meaningful CPAP.

Purpose To investigate if respiratory mechanics and other baseline characteristics are predictors of patient-ventilator asynchrony and to evaluate the relationship between asynchrony during assisted ventilation and clinical outcomes. Methods We performed a prospective cohort study in patients under mechanical ventilation (MV). Baseline measurements included severity of illness and respiratory mechanics. The primary outcome was the Asynchrony Index (AI), defined as the number of asynchronous events divided by the number of ventilator cycles and wasted efforts. We recorded ventilator waveforms throughout the entire period of MV. Results We analyzed 11,881 h of MV from 103 subjects. Median AI during the entire period of MV was 5.1% (IQR:2.6–8.7). Intrinsic PEEP was associated with AI (OR:1.72, 95%CI:1.1–2.68), but static compliance and airway resistance were not. Simplified Acute Physiology Score 3 (OR:1.03, 95%CI:1–1.06) was also associated with AI. Median AI was higher during assisted (5.4%, IQR:2.9–9.1) than controlled (2%, IQR:0.6–4.9) ventilation, and 22% of subjects had high incidence of asynchrony (AI≥10%). Subjects with AI≥10% had more extubation failure (33%) than patients with AI Conclusions Predictors of high incidence of asynchrony were severity of illness and intrinsic PEEP. High incidence of asynchrony was associated with extubation failure, but not mortality. Trial registration: ClinicalTrials.gov , NCT02687802

A brief review of how central adiposity affects intrathoracic pressures and its effects on spontaneous breathing and artificial ventilation.

BACKGROUND: This was a pilot study to analyze the effects of tracheostomy on patient-ventilator asynchronies and respiratory system mechanics. Data were extracted from an ongoing prospective, real-world database that stores continuous output from ventilators and bedside monitors. Twenty adult subjects were on mechanical ventilation and were tracheostomized during an ICU stay: 55% were admitted to the ICU for respiratory failure and 35% for neurologic conditions; the median duration of mechanical ventilation before tracheostomy was 12 d; and the median duration of mechanical ventilation was 16 d. METHODS: We compared patient-ventilator asynchronies (the overall asynchrony index and the rates of specific asynchronies) and respiratory system mechanics (respiratory-system compliance and airway resistance) during the 24 h before tracheostomy versus the 24 h after tracheostomy. We analyzed possible differences in these variables among the subjects who underwent surgical versus percutaneous tracheostomy. To compare longitudinal changes in the variables, we used linear mixed-effects models for repeated measures along time in different observation periods. A total of 920 h of mechanical ventilation were analyzed. RESULTS: Respiratory mechanics and asynchronies did not differ significantly between the 24-h periods before and after tracheostomy: compliance of the respiratory system median (IQR) (47.9 [41.3 – 54.6] mL/cm H(2)O vs 47.6 [40.9 – 54.3] mL/cm H(2)O; P = .94), airway resistance (9.3 [7.5 – 11.1] cm H(2)O/L/s vs 7.0 [5.2 – 8.8] cm H(2)O/L/s; P = .07), asynchrony index (2.0% [1.1 – 3.6%] vs 4.1% [2.3 – 7.6%]; P = .09), ineffective expiratory efforts (0.9% [0.4 – 1.8%] vs 2.2% [1.0 – 4.4%]; P = .08), double cycling (0.5% [0.3 – 1.0%] vs 0.9% [0.5 – 1.9%]; P = .24), and percentage of air trapping (7.6% [4.2 – 13.8%] vs 10.6% [5.9 – 19.2%]; P = .43). No differences in respiratory mechanics or patient-ventilator asynchronies were observed between percutaneous and surgical procedures. CONCLUSIONS: Tracheostomy did not affect patient-ventilator asynchronies or respiratory mechanics within 24 h before and after the procedure

OBJECTIVES: To develop a scoring model for stratifying patients with acute respiratory distress syndrome into risk categories (Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score) for early prediction of death in the ICU, independent of the underlying disease and cause of death. DESIGN: A development and validation study using clinical data from four prospective, multicenter, observational cohorts. SETTING: A network of multidisciplinary ICUs. PATIENTS: One-thousand three-hundred one patients with moderate-to-severe acute respiratory distress syndrome managed with lung-protective ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The study followed Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis guidelines for prediction models. We performed logistic regression analysis, bootstrapping, and internal-external validation of prediction models with variables collected within 24 hours of acute respiratory distress syndrome diagnosis in 1,000 patients for model development. Primary outcome was ICU death. The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score was based on patient's age, number of extrapulmonary organ failures, values of end-inspiratory plateau pressure, and ratio of Pao2to Fio2assessed at 24 hours of acute respiratory distress syndrome diagnosis. The pooled area under the receiver operating characteristic curve across internal-external validations was 0.860 (95% CI, 0.831-0.890). External validation in a new cohort of 301 acute respiratory distress syndrome patients confirmed the accuracy and robustness of the scoring model (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.829-0.911). The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score stratified patients in three distinct prognostic classes and achieved better prediction of ICU death than ratio of Pao2to Fio2at acute respiratory distress syndrome onset or at 24 hours, Acute Physiology and Chronic Health Evaluation II score, or Sequential Organ Failure Assessment scale. CONCLUSIONS: The Stratification for identification of Prognostic categories In the acute RESpiratory distress syndrome score represents a novel strategy for early stratification of acute respiratory distress syndrome patients into prognostic categories and for selecting patients for therapeutic trials.

Pendelluft phenomenon is defined as the displacement of gas from a more recruited nondependent (ND) lung region to a less recruited dependent (D) lung region. This phenomenon may cause lung injury. Thus, a lung model for pendelluft was established, and the effects of ventilatory settings on pendelluft were examined.Two sets of the twin-bellows-type training test lung (TTL) model were utilized. One set of bellows simulated the diaphragm, and the other simulated the lung. One TTL model represented the ND region, and the other represented the D region. The lung bellows were connected to each other and were ventilated with 1 ventilator. The diaphragm bellows were ventilated with 2 synchronized ventilators that regulated pleural pressure levels. We simulated pendelluft by applying different pleural pressure levels to the D and ND bellows. The increment of the tidal volume in the D region from the "no breathing effort" condition was defined as the pendelluft volume. The effects of ventilator settings, such as ventilatory modes, triggering sensitivity, inspiratory pressurization, and inspiratory cycling-off, were examined. The changes in tidal volumes in the D region based on the control settings were compared to assess the severity of pendelluft.The gas flow from the D region to the ND region was found to be essential in pendelluft, but the severity of this phenomenon was not always proportional to gas flows. The severity increased with the increase in the differences in pleural pressure levels between the ND and D regions, and it was amplified by the difference in lung mechanics between the ND and D regions. However, the ventilator settings had minimal effect on the severity of pendelluft.The pendelluft was affected by the heterogeneity of lung mechanics and pleural pressure. Furthermore, a minimal association was observed between the ventilator settings and the severity of pendelluft.

Background Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). Methods This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients. Results Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4–8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. Conclusions In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.

Obesity prevalence is increasing in most countries in the world. In the United States, 42% of the population is obese (body mass index (BMI) 30) and 9.2% is obese class III (BMI 40). One of the greatest challenges in critically ill patients with obesity is the optimization of mechanical ventilation. The goal of this review is to describe respiratory physiologic changes in patients with obesity and discuss possible mechanical ventilation strategies to improve respiratory function.Individualized mechanical ventilation based on respiratory physiology after a decremental positive end-expiratory pressure (PEEP) trial improves oxygenation and respiratory mechanics. In a recent study, mortality of patients with respiratory failure and obesity was reduced by about 50% when mechanical ventilation was associated with the use of esophageal manometry and electrical impedance tomography (EIT).Obesity greatly alters the respiratory system mechanics causing atelectasis and prolonged duration of mechanical ventilation. At present, novel strategies to ventilate patients with obesity based on individual respiratory physiology showed to be superior to those based on standard universal tables of mechanical ventilation. Esophageal manometry and EIT are essential tools to systematically assess respiratory system mechanics, safely adjust relatively high levels of PEEP, and improve chances for successful weaning.

Independent lung ventilation, though infrequently used in the critical care setting, has been reported as a rescue strategy for patients in respiratory failure resulting from severe unilateral lung pathology. This involves isolating and ventilating the right and left lung differently, using separate ventilators. Here, we describe our experience with independent lung ventilation in a patient with unilateral diffuse alveolar hemorrhage, who presented with severe hypoxemic respiratory failure despite maximal ventilatory support. Conventional ventilation in this scenario leads to preferential distribution of tidal volume to the non-diseased lung causing over distension and inadvertent volume trauma. Since each lung has a different compliance and respiratory mechanics, instituting separate ventilation strategies to each lung could potentially minimize lung injury. Based on review of literature, we provide a detailed description of indications and procedures for establishing independent lung ventilation, and also provide an algorithm for management and weaning a patient from independent lung ventilation.

Efforts to improve health equity may be advanced by understanding health care providers' perceptions of the causes of health inequalities. Drawing on data from in-depth interviews with nurses and registered respiratory therapists (RRTs) who served on intensive care units (ICUs) during the first surge of the pandemic, this paper examines how frontline providers perceive and attribute the unequal impacts of COVID-19. It shows that nurses and RRTs quickly perceived the pandemic's disproportionate burden on Black and Latinx individuals and families. Providers attribute these inequalities to the social determinants of health, and also raise questions about how barriers to healthcare access may have made some patients more vulnerable to the worst consequences of COVID-19. Providers' perceptions of inequality and its consequences on COVID-19 ICUs were emotionally impactful and distressing, suggesting that this is a critical moment for offering clinicians practical strategies for understanding and addressing the persistent structural inequities that cause racial inequalities in health.

Background Increased pleural pressure affects the mechanics of breathing of people with class III obesity (BMI > 40 kg/m2). Research Question What are the acute effects of CPAP titrated to match pleural pressure on cardiopulmonary function in spontaneously breathing patients with class III obesity? Study design and Methods We enrolled six participants with BMI within normal range (control participants, group I) and 12 patients with class III obesity (group II) divided into subgroups: IIa, BMI of 40 to 50 kg/m2; and IIb, BMI of ≥ 50 kg/m2. The study was performed in two phases: in phase 1, participants were supine and breathing spontaneously at atmospheric pressure, and in phase 2, participants were supine and breathing with CPAP titrated to match their end-expiratory esophageal pressure in the absence of CPAP. Respiratory mechanics, esophageal pressure, and hemodynamic data were collected, and right heart function was evaluated by transthoracic echocardiography. Results The levels of CPAP titrated to match pleural pressure in group I, subgroup IIa, and subgroup IIb were 6 ± 2 cmH2O, 12 ± 3 cmH2O, and 18 ± 4 cmH2O, respectively. In both subgroups IIa and IIb, CPAP titrated to match pleural pressure decreased minute ventilation (IIa, P = .03; IIb, P = .03), improved peripheral oxygen saturation (IIa, P = .04; IIb, P = .02), improved homogeneity of tidal volume distribution between ventral and dorsal lung regions (IIa, P = .22; IIb, P = .03), and decreased work of breathing (IIa, P Interpretation In ambulatory patients with class III obesity, CPAP titrated to match pleural pressure decreased work of breathing and improved respiratory mechanics while maintaining hemodynamic stability, without impairing right heart function. Trial Registry ClinicalTrials.gov; No.: NCT02523352; URL: www.clinicaltrials.gov

Treatment options are limited for patients with respiratory failure due to coronavirus disease 2019. Conventional oxygen therapy and awake proning are options, but the use of high-flow nasal cannula and continuous positive airway pressure are controversial. There is an urgent need for effective rescue therapies. Our aim is to evaluate the role of inhaled nitric oxide 160 ppm as a possible rescue therapy in nonintubated coronavirus disease 2019 patients. Design Retrospective evaluation of coronavirus disease 2019 patients in respiratory distress receiving nitric oxide gas as rescue therapy. Setting Massachusetts General Hospital, between March 18, 2020, and May 20, 2020, during the local coronavirus disease 2019 surge. Patients Coronavirus disease 2019 patients at high risk for acute hypoxemic respiratory failure with worsening symptoms despite use of supplemental oxygen and/or awake proning. Interventions Patients received nitric oxide at concentrations of 160 ppm for 30 minutes twice per day via a face mask until resolution of symptoms, discharge, intubation, or the transition to comfort measures only. Measurements and main results Between March 18, 2020, and May 20, 2020, five patients received nitric oxide inhalation as a rescue therapy for coronavirus disease 2019 at Massachusetts General Hospital. All received at least one dosage. The three patients that received multiple treatments (ranging from five to nine) survived and were discharged home. Maximum methemoglobin concentration after 30 minutes of breathing nitric oxide was 2.0% (1.7-2.3%). Nitrogen dioxide was below 2 ppm. No changes in mean arterial pressure or heart rate were observed during or after nitric oxide treatment. Oxygenation and the respiratory rate remained stable during and after nitric oxide treatments. For two patients, inflammatory marker data were available and demonstrate a reduction or a cessation of escalation after nitric oxide treatment. Conclusions Nitric oxide at 160 ppm may be an effective adjuvant rescue therapy for patients with coronavirus disease 2019.

Background: We aimed to identify the prevalence of acute hypoxaemic respiratory failure (AHRF) in the intensive care unit (ICU) and its associated mortality. The secondary aim was to describe ventilatory management as well as the use of rescue therapies. Methods: Multi-centre prospective study in nine hospitals in Wales, UK, over 2-month periods. All patients admitted to an ICU were screened for AHRF and followed-up until discharge from the ICU. Data were collected from patient charts on patient demographics, clinical characteristics, management and outcomes. Results: Out of 2215 critical care admissions, 886 patients received mechanical ventilation. A total of 197 patients met inclusion criteria and were recruited. Seventy (35.5%) were non-survivors. Non-survivors were significantly older, had higher SOFA scores and received more vasopressor support than survivors. Twenty-five (12.7%) patients who fulfilled the Berlin definition of acute respiratory distress syndrome (ARDS) during the ICU stay without impact on overall survival. Rescue therapies were rarely used. Analysis of ventilation showed that median Vt was 7.1 mL/kg PBW (IQR 5.9–9.1) and 21.3% of patients had optimal ventilation during their ICU stay. Conclusions: One in four mechanically ventilated patients have AHRF. Despite advances of care and better, but not optimal, utilisation of low tidal volume ventilation, mortality remains high.

Supplemental Digital Content is available in the text., Objectives: To design and test a ventilator circuit that can be used for ventilation of two or more patients with a single ventilator, while allowing individualization of tidal volume, fractional concentration of oxygen, and positive end-expiratory pressure to each patient, irrespective of the other patient’s respiratory system mechanics. Design: Description and proof of concept studies. Settings: Respiratory therapy laboratory. Subjects: Ventilation of mechanical test lungs. Interventions: Following a previously advocated design, we used components readily available in our hospital to assemble two “bag-in-a-box” breathing circuits. Each patient circuit consisted of a flexible bag in a rigid container connected via one-way valve to a test lung, along with an inline positive end-expiratory pressure valve, connected to the ventilator’s expiratory limb. Compressed gas fills the bags during “patient” exhalation. During inspiration, gas from the ventilator, in pressure control mode, enters the containers and displaces gas from the bags to the test lungs. We varied tidal volume, “respiratory system” compliance, and positive end-expiratory pressure in one lung and observed the effect on the tidal volume of the other. Measurements and Main Results: We were able to obtain different tidal volume, dynamic driving pressure, and positive end-expiratory pressure in the two lungs under widely different compliances in both lungs. Complete obstruction, or disconnection at the circuit connection to one test lung, had minimal effect (< 5% on average) on the ventilation to the co-ventilated lung. Conclusions: A secondary circuit “bag-in-the-box” system enables individualized ventilation of two lungs overcoming many of the concerns of ventilating more than one patient with a single ventilator.

BACKGROUND: A lung-protective mechanical ventilation strategy has become the hallmark of ventilation management for patients with acute respiratory failure. However, some patients progress to more severe forms of acute respiratory failure with refractory hypoxemia. In such circumstances, individualized titration of mechanical ventilation according to the patient9s specific respiratory and cardiovascular pathophysiology is desirable. A lung rescue team (LRT) was recently established at our institution to improve the medical care of patients with acute respiratory failure when conventional treatment fails. The aim of this report is to describe the consultation processes, the cardiopulmonary assessment, and the procedures of the LRT. METHODS: This was a retrospective review of the LRT management of patients with acute respiratory failure and refractory hypoxemia at Massachusetts General Hospital in Boston, Massachusetts. The LRT is composed of a critical care physician, the ICU respiratory therapist on duty, the ICU nurse on duty, and 2 critical care fellows. In the LRT approach, respiratory mechanics are evaluated through lung recruitment maneuvers and decremental PEEP trials by means of 3 tools: esophageal manometry, echocardiography, and electrical impedance tomography lung imaging. RESULTS: The LRT was consulted 89 times from 2014 to 2019 for evaluation and management of severely critically ill patients with acute respiratory failure and refractory hypoxemia on mechanical ventilation. The LRT was requested a median of 2 (interquartile range 1–6) d after intubation to optimize mechanical ventilation and to titrate PEEP in 77 (86%) subjects, to manage ventilation in 8 (9%) subjects on extracorporeal membrane oxygenation (ECMO), and to manage weaning strategy from mechanical ventilation in 4 (5%) subjects. The LRT found consolidations with atelectasis responsive to recruitment maneuvers in 79% (n = 70) of consultations. The LRT findings translated into a change of care in 81% (n = 72) of subjects. CONCLUSIONS: The LRT individualized the management of severe acute respiratory failure. The LRT consultations were shown to be effective, safe, and efficient, with an impact on decision-making in the ICU.

Recently, we developed a novel endotracheal catheter with functional cuff (ECFC). Using such an ECFC and a regular ICU ventilator, we were able to generate clinically relevant tidal volume in a lung model and adult human sized animal. This ECFC allows co-axial ventilation without using a jet ventilator. The aim of this study was to determine if ECFC also could generate clinically relevant positive end expiratory pressure (PEEP). The experiment was conducted on a model lung and artificial trachea. Lung model respiratory mechanics were set to simulate those of an adult human being. The tip of the distal end of ECFC 14 or 19 Fr catheter was positioned in the artificial trachea 3 cm above the carina. The proximal end of ECFC was connected to an ordinary ICU ventilator. With 14 Fr catheter at respiratory rate 10 bpm, PEEP 0, 2.9, 8.2, 12.9 cmH2O was generated at preset PEEP 0, 5, 10, 15 cmH2O respectively and tidal volume was up to 393.4 ml. With 19 Fr catheter, PEEP was 0, 2.8, 7.6, 12.3 cmH2O, at preset PEEP 0, 5, 10, 15 cmH2O respectively and the tidal volume was up to 667.3 ml. With 14 Fr catheter at respiratory rate 20 bpm, PEEP was 0, 3.9, 9.6, 14.6 cmH2O at preset PEEP 0, 5, 10, 15 cmH2O respectively and tidal volume was up to 188.8 ml. With 19 Fr catheter, PEEP was 0, 3.6, 8.9, 13 cmH2O, at preset PEEP 0, 5, 10, 15 cmH2O respectively and tidal volume was up to 345.3 ml. ECFC enables clinicians to generate not only adequate tidal volume but also clinically relevant PEEP via co-axial ventilation using an ordinary ICU ventilator.

Background Intraoperative use of positive end-expiratory pressure (PEEP) has a protective effect in patients with acute lung injury and is recommended during anesthesia to minimize postoperative pulmonary complications. However, high levels of pressure might also cause harm to the lung because of overdistension. This retrospective study was designed to compare the effect of low and high levels of PEEP on the risk of postoperative pulmonary complications in patients with normal lung function who were undergoing an elective craniotomy. Methods Two thousand four hundred thirty-seven patients without any pre-existing respiratory disease, who underwent an elective craniotomy, were hospitalized from January 1, 2008, to December 31, 2012. The patients were divided into 2 groups according to the application of an intraoperative PEEP Results One thousand twenty-three (42%) of 2437 patients were in the low group, and 1414 patients (58%) were in the high group. Patients in the low group did not show any difference in the incidence of postoperative pneumonia (P = 0.523) or the requirement of postoperative reintubation and MV (P = 0.999) compared with those in the high group. The incidence of reintubation and MV is significantly associated with postoperative pneumonia (P Conclusions Low and high levels of PEEP show similar incidences of postoperative pneumonia and requirement of postoperative NIV or invasive MV in patients with normal function of the lungs undergoing elective craniotomy.

Purpose of review The modern operating room ventilators have become very sophisticated and many of their features are comparable with those of an ICU ventilator. To fully utilize the functionality of modern operating room ventilators, it is important for clinicians to understand in depth the working principle of these ventilators and their functionalities. Recent findings Piston ventilators have the advantages of delivering accurate tidal volume and certain flow compensation functions. Turbine ventilators have great ability of flow compensation. Ventilation modes are mainly volume-based or pressure-based. Pressure-based ventilation modes provide better leak compensation than volume-based. The integration of advanced flow generation systems and ventilation modes of the modern operating room ventilators enables clinicians to provide both invasive and noninvasive ventilation in perioperative settings. Ventilator waveforms can be used for intraoperative neuromonitoring during cervical spine surgery. Summary The increase in number of new features of modern operating room ventilators clearly creates the opportunity for clinicians to optimize ventilatory care. However, improving the quality of ventilator care relies on a complete understanding and correct use of these new features. VIDEO ABSTRACT: http://links.lww.com/COAN/A47.

Background Upper airway obstruction occurs commonly after induction of general anaesthesia. It is the major cause of difficult mask ventilation. Objectives The aim of this study was to determine whether head rotation improves the efficiency of mask ventilation of anaesthetised apnoeic adults. Design A randomised, crossover study. Setting Single university teaching hospital. Patients Forty patients, aged 18 to 75 years with a BMI 18.5 to 35.0 kg m requiring general anaesthesia for elective surgery were recruited and randomised into two groups. Interventions Once apnoeic after induction of general anaesthesia, face mask ventilation began with pressure controlled ventilation, at a peak inspiratory pressure of 15 cmH2O. Each patient was ventilated for three 1-min intervals with the head position alternated every minute: group A, mask ventilation was performed with a neutral head position for 1 min, followed by an axial head position rotated 45° to the right for 1 min and then returned to the neutral position for another 1 min. In group B, the sequence of head positioning was rotated → neutral → rotated. Main outcome measures Expiratory tidal volume, measured with a respiratory inductive plethysmograph. Results Two patients were excluded due to protocol violation; thus, data from 38 patients were analysed. The mean expiratory tidal volume was significantly higher in the rotated head position than in the neutral position (612.6 vs. 544.0 ml: difference [95% confidence interval], 68.6 [46.8 to 90.4] ml, P Conclusion Head rotation of 45° in anaesthetised apnoeic adults significantly increases the efficiency of mask ventilation compared with the neutral head position. Head rotation is an effective alternative to improve mask ventilation if airway obstruction is encountered. Trial registration ClinicalTrials.gov identifier: NCT02755077.

BACKGROUND: Cuff design affects microaspiration, a risk factor for pneumonia. We questioned whether the PneuX low-volume fold-free cuff design would prevent cuff leakage and maintain the same tracheal wall pressure as high-volume, low-pressure (HVLP) cuffs. METHODS: We evaluated 4 HVLP-cuffed endotracheal tubes (ETTs), Hi-Lo (polyvinyl chloride [PVC]), Microcuff (polyurethane [PU]), SealGuard (PU + tapered), and TaperGuard (PVC + tapered), and the PneuX with its dedicated tracheal seal monitor. In Part 1, we determined tracheal wall pressure using each cuff9s capacity to support water columns across recommended intracuff pressures. In Part 2, we evaluated the tracheal seal monitor function at recommended settings. In Part 3, we compared leakage volumes of all ETTs during 30 min of simulated mechanical ventilation or during 8 h if no leak occurred. Parts 1 and 3 were performed with/without lubrication and PEEP. RESULTS: In Part 1, PneuX cuffs exerted an average tracheal wall pressure of 27.4 ± 2.4 cm H2O at the recommended intracuff pressure of approximately 80 cm H2O. Tracheal wall pressure did not differ among HVLP cuffs (19.6 ± 1.4 to 29.5 ± 1.4 cm H2O). In Part 2, preinflation intracuff pressure affected the time to obtain tracheal seal monitor pressure attainment (P CONCLUSIONS: The PneuX cuff generally exerted acceptable tracheal wall pressure, but the tracheal wall pressure monitor allowed pressures exceeding 30 cm H2O in some trials and was the only ETT to prevent leak in all tests. For HVLP cuffs, leak was reduced by PU and PEEP and eliminated by lubrication.

The acute respiratory distress syndrome (ARDS) is an acute and intense inflammatory process of the lungs that develops in response to pulmonary and systemic insults to the alveolar-capillary membrane, resulting in increased vascular permeability and development of interstitial and alveolar edema. Although ARDS is clinically characterized by acute hypoxemic respiratory failure refractory to oxygen therapy, over the years we have used several different diagnostic schemas, all based on a combination of clinical, oxygenation, radiographic, and hemodynamic abnormalities to identify these patients (1,2).

IntroductionPostoperative acute kidney injury (AKI) is a common complication in cardiac surgery. Levels of intravascular haemolysis are strongly associated with postoperative AKI and with prolonged (>90 min) use of cardiopulmonary bypass (CPB). Ferrous plasma haemoglobin released into the circulation acts as a scavenger of nitric oxide (NO) produced by endothelial cells. Consequently, the vascular bioavailability of NO is reduced, leading to vasoconstriction and impaired renal function. In patients with cardiovascular risk factors, the endothelium is dysfunctional and cannot replenish the NO deficit. A previous clinical study in young cardiac surgical patients with rheumatic fever, without evidence of endothelial dysfunction, showed that supplementation of NO gas decreases AKI by converting ferrous plasma haemoglobin to ferric methaemoglobin, thus preserving vascular NO. In this current trial, we hypothesised that 24 hours administration of NO gas will reduce AKI following CPB in patients with endothelial dysfunction.MethodsThis is a single-centre, randomised (1:1) controlled, parallel-arm superiority trial that includes patients with endothelial dysfunction, stable kidney function and who are undergoing cardiac surgery procedures with an expected CPB duration >90 min. After randomisation, 80 parts per million (ppm) NO (intervention group) or 80 ppm nitrogen (N2, control group) are added to the gas mixture. Test gases (N2or NO) are delivered during CPB and for 24 hours after surgery. The primary study outcome is the occurrence of AKI among study groups. Key secondary outcomes include AKI severity, occurrence of renal replacement therapy, major adverse kidney events at 6 weeks after surgery and mortality. We are recruiting 250 patients, allowing detection of a 35% AKI relative risk reduction, assuming a two-sided error of 0.05.Ethics and disseminationThe Partners Human Research Committee approved this trial. Recruitment began in February 2017. Dissemination plans include presentations at scientific conferences, scientific publications and advertising flyers and posters at Massachusetts General Hospital.Trial registration numberNCT02836899.

The rate of re-intubation after endotracheal extubation for all indications is estimated at ∼20%. This high rate is related, in part, to the development of postoperative complications that leads to acute respiratory failure that requires re-intubation. In general, 5-10% of all surgical patients develop postoperative respiratory failure, and, in patients who require abdominal surgery, up to 40% develop respiratory failure. The forms of respiratory support that have been shown to be most effective in managing postextubation respiratory failure and preventing re-intubation are noninvasive ventilation, CPAP, and high-flow nasal cannula. From an analysis of the data, it is clear that patients at high risk of re-intubation require CPAP, noninvasive ventilation, or high-flow nasal cannula after extubation to allow for a smooth transition to spontaneous breathing and to minimize the need for re-intubation. CPAP is most indicated in patients with atelectasis in which high levels of PEEP are needed, noninvasive ventilation is indicated in the patient unable to maintain an adequate minute ventilation without excessive work of breathing, and high-flow nasal cannula is indicated in the patient with severe hypoxemia that was not a result of marked atelectasis or severe ARDS. It is also clear that there are insufficient data to support the use of any of these therapies in patients at low risk for re-intubation or the development of postoperative pulmonary complications.

BACKGROUND: High-flow nasal cannulas (HFNC) have been increasingly used in the pediatric critical care patient population. There are different theories about the mechanism by which HFNC reduces work of breathing, including diminishing upper airway dead space by the washout of carbon dioxide. However, one of the likely primary mechanisms by which HFNC reduces work of breathing is by generating PEEP. There are limited data assessing the PEEP delivered by moderate flows (8 –50 L/min) of HFNC, which are used most commonly in pediatric patients. METHODS: Pediatric upper-airway models were created with 5 different nares produced by a 3-dimensional printer and connected to a lung simulator. Age-specific flows were delivered via the 5 different setups. Pressure throughout the simulated airway was measured at HFNC flows of 6 – 60 L/min with 25%, 50%, and 75% air leak to simulate open-mouth breathing. RESULTS: PEEPs of 1.2–36 cm H2O were generated with HFNC flows of 6 – 60 L/min. In general, for each specific cannula, increasing the flow and decreasing the air leak resulted in higher levels of PEEP delivered (P 10% difference). Changes in lung mechanics as generated by the lung simulator to simulate different patient ages resulted in the establishment of different levels of PEEP. CONCLUSIONS: HFNCs deliver varying amounts of PEEP at the alveolar level with flows of 6 – 60 L/min. Increasing flow and decreasing leak resulted in the generation of greater PEEP. PEEP levels differed across cannulas and model weights at the same leak level, likely due to differences in the nasal interface between the HFNC device and the model nares.

IntroductionPatient-ventilator asynchrony is common during the entire period of invasive mechanical ventilation (MV) and is associated with worse clinical outcomes. However, risk factors associated with asynchrony are not completely understood. The main objectives of this study are to estimate the incidence of asynchrony during invasive MV and its association with respiratory mechanics and other baseline patient characteristics.Methods and analysisWe designed a prospective cohort study of patients admitted to the intensive care unit (ICU) of a university hospital. Inclusion criteria are adult patients under invasive MV initiated for less than 72 hours, and with expectation of remaining under MV for more than 24 hours. Exclusion criteria are high flow bronchopleural fistula, inability to measure respiratory mechanics and previous tracheostomy. Baseline assessment includes clinical characteristics of patients at ICU admission, including severity of illness, reason for initiation of MV, and measurement of static mechanics of the respiratory system. We will capture ventilator waveforms during the entire MV period that will be analysed with dedicated software (Better Care, Barcelona, Spain), which automatically identifies several types of asynchrony and calculates the asynchrony index (AI). We will use a linear regression model to identify risk factors associated with AI. To assess the relationship between survival and AI we will use Kaplan-Meier curves, log rank tests and Cox regression. The calculated sample size is 103 patients. The statistical analysis will be performed by the software R Programming (www.R-project.org) and will be considered statistically significant if the p value is less than 0.05.Ethics and disseminationThe study was approved by the Ethics Committee of Instituto do Coração, School of Medicine, University of São Paulo, Brazil, and informed consent was waived due to the observational nature of the study. We aim to disseminate the study findings through peer-reviewed publications and national and international conference presentations.Trial registration numberNCT02687802; Pre-results.

BACKGROUND: Biofilm on the surface of endotracheal tubes (ETTs) is associated with ventilator-associated pneumonia. The use of silver-coated ETTs has been suggested to reduce the occurrence of ventilator-associated pneumonia by preventing biofilm formation. However, mucus accumulation can reduce the antibacterial activity of silver-coated ETTs by isolating bacterial colonies from the silver surface. We hypothesized that, in mechanically ventilated subjects, periodic removal of secretions through the use of a cleaning device would enhance the antimicrobial properties of silver-coated ETTs and thus reduce bacterial colonization. METHODS: Subjects were randomized to either standard suctioning (blind tracheal suctioning, control group) or blind tracheal suctioning plus cleaning maneuver every 8 h (treatment group). Tracheal aspirates were collected immediately before extubation for microbiological culture. After extubation, ETTs were collected for both cultural and non-cultural microbiological analysis and biofilm isolation. RESULTS: 39 subjects expected to be ventilated for > 48 h were enrolled; 36 ETTs (18 control, 18 treatment) and 29 tracheal samples (15 control, 14 treatment) were collected. Among the ETTs positive for bacterial colonization (15 vs 9, P =.18), cleaning maneuvers did not reduce microbial load, shown as the decimal logarithm of colony-forming units (CFU) per mL (1.6 ± 1.2 vs 0.9 ± 1.2 logCFU/mL, P =.15). There was a trend toward decreased biofilm deposition (439.5 ± 29.0 vs 288.9 ± 157.7 mg, P =.09) in the treated ETTs. No significant differences were observed in the number of positive tracheal aspirates (13 vs 10, P =.39) or in the microbial load (4.8 ± 4.0 vs 4.2 ± 3.8 logCFU/mL, P =.70) of tracheal secretions. Finally, no differences in the microbial load of Gram-positive organisms, Gram-negative organisms, or yeasts were found between the ETTs and tracheal aspirates of the 2 groups. CONCLUSIONS: In 39 critically-ill subjects intubated with silver-coated ETTs, periodic cleaning maneuvers did not decrease bacterial colonization of the ETTs and did not lower respiratory tract colonization compared to the standard suctioning. (Clinicaltrials.gov reg-istration NCT02120001.)