Expiratory flow limitation during mechanical ventilation: real-time detection and physiological subtypes.

BACKGROUND: Tidal expiratory flow limitation (EFLT) complicates the delivery of mechanical ventilation but is only diagnosed by performing specific manoeuvres. Instantaneous analysis of expiratory resistance (Rex) can be an alternative way to detect EFLT without changing ventilatory settings. This study aimed to determine the agreement of EFLT detection by Rex analysis and the PEEP reduction manoeuvre using contingency table and agreement coefficient. The patterns of Rex were explored. METHODS: Medical patients ≥ 15-year-old receiving mechanical ventilation underwent a PEEP reduction manoeuvre from 5 cmH2O to zero for EFLT detection. Waveforms were recorded and analyzed off-line. The instantaneous Rex was calculated and was plotted against the volume axis, overlapped by the flow-volume loop for inspection. Lung mechanics, characteristics of the patients, and clinical outcomes were collected. The result of the Rex method was validated using a separate independent dataset. RESULTS: 339 patients initially enrolled and underwent a PEEP reduction. The prevalence of EFLT was 16.5%. EFLT patients had higher adjusted hospital mortality than non-EFLT cases. The Rex method showed 20% prevalence of EFLT and the result was 90.3% in agreement with PEEP reduction manoeuvre. In the validation dataset, the Rex method had resulted in 91.4% agreement. Three patterns of Rex were identified: no EFLT, early EFLT, associated with airway disease, and late EFLT, associated with non-airway diseases, including obesity. In early EFLT, external PEEP was less likely to eliminate EFLT. CONCLUSIONS: The Rex method shows an excellent agreement with the PEEP reduction manoeuvre and allows real-time detection of EFLT. Two subtypes of EFLT are identified by Rex analysis. TRIAL REGISTRATION: Clinical trial registered with www.thaiclinicaltrials.org (TCTR20190318003). The registration date was on 18 March 2019, and the first subject enrollment was performed on 26 March 2019.

Outcomes after Introduction of Minimally Invasive Surfactant Therapy in Two Australian Tertiary Neonatal Units.

OBJECTIVE: To assess the procedural and clinical outcomes associated with the introduction of minimally invasive surfactant therapy (MIST) into standard care at 2 tertiary Australian neonatal intensive care units. STUDY DESIGN: A prospective audit was designed before the introduction of MIST in 2018, with data collected over a period of 18 months. Procedural data were completed by the clinical team performing MIST, including clinical observations, medication use, and adverse events. The audit team collected demographic data and subsequent clinical outcomes from medical records. RESULTS: There were 135 MIST procedures recorded in 122 infants. For the included infants, the median gestation was 302/7 weeks (IQR, 276/7 to 322/7 weeks) and birth weight was 1439 g (IQR, 982-1958 g). During the MIST procedure, desaturation to a peripheral oxygen saturation of <80% was common, occurring in 75.2% of procedures. Other adverse events included need for positive pressure ventilation (10.6%) and bradycardia <100 beats per minute (13.3%). The use of atropine premedication was associated with a significantly lower incidence of bradycardia: 8.6% vs 52.9% (P < .01). Senior clinicians demonstrated higher rates of procedural success. The majority of infants (63.9%) treated with MIST did not require subsequent intubation and mechanical ventilation. CONCLUSIONS: MIST can be successfully introduced in neonatal units with limited experience of this technique. The use of atropine premedication decreases the incidence of bradycardia during the procedure. Success rates can be optimized by limiting MIST to clinicians with greater competence in endotracheal intubation.

Automated detection and quantification of reverse triggering effort under mechanical ventilation.

BACKGROUND: Reverse triggering (RT) is a dyssynchrony defined by a respiratory muscle contraction following a passive mechanical insufflation. It is potentially harmful for the lung and the diaphragm, but its detection is challenging. Magnitude of effort generated by RT is currently unknown. Our objective was to validate supervised methods for automatic detection of RT using only airway pressure (Paw) and flow. A secondary objective was to describe the magnitude of the efforts generated during RT. METHODS: We developed algorithms for detection of RT using Paw and flow waveforms. Experts having Paw, flow and esophageal pressure (Pes) assessed automatic detection accuracy by comparison against visual assessment. Muscular pressure (Pmus) was measured from Pes during RT, triggered breaths and ineffective efforts. RESULTS: Tracings from 20 hypoxemic patients were used (mean age 65 ± 12 years, 65% male, ICU survival 75%). RT was present in 24% of the breaths ranging from 0 (patients paralyzed or in pressure support ventilation) to 93.3%. Automatic detection accuracy was 95.5%: sensitivity 83.1%, specificity 99.4%, positive predictive value 97.6%, negative predictive value 95.0% and kappa index of 0.87. Pmus of RT ranged from 1.3 to 36.8 cmH20, with a median of 8.7 cmH20. RT with breath stacking had the highest levels of Pmus, and RTs with no breath stacking were of similar magnitude than pressure support breaths. CONCLUSION: An automated detection tool using airway pressure and flow can diagnose reverse triggering with excellent accuracy. RT generates a median Pmus of 9 cmH2O with important variability between and within patients. TRIAL REGISTRATION: BEARDS, NCT03447288.

Early individualized positive end-expiratory pressure guided by electrical impedance tomography in acute respiratory distress syndrome: a randomized controlled clinical trial.

BACKGROUND: Individualized positive end-expiratory pressure (PEEP) by electrical impedance tomography (EIT) has potential interest in the optimization of ventilation distribution in acute respiratory distress syndrome (ARDS). The aim of the study was to determine whether early individualized titration of PEEP with EIT improved outcomes in patients with ARDS. METHODS: A total of 117 ARDS patients receiving mechanical ventilation were randomly assigned to EIT group (n = 61, PEEP adjusted based on ventilation distribution) or control group (n = 56, low PEEP/FiO2 table). The primary outcome was 28-day mortality. Secondary and exploratory outcomes were ventilator-free days, length of ICU stay, incidence of pneumothorax and barotrauma, and difference in Sequential Organ Failure Assessment (SOFA) score at day 1 (ΔD1-SOFA) and day 2 (ΔD2-SOFA) compared with baseline. MEASUREMENTS AND MAIN RESULTS: There was no statistical difference in the value of PEEP between the EIT group and control group, but the combination of PEEP and FiO2 was different between groups. In the control group, a significantly positive correlation was found between the PEEP value and the corresponding FiO2 (r = 0.47, p < 0.00001) since a given matched table was used for PEEP settings. Diverse combinations of PEEP and FiO2 were found in the EIT group (r = 0.05, p = 0.68). There was no significant difference in mortality rate (21% vs. 27%, EIT vs. control, p = 0.63), ICU length of stay (13.0 (7.0, 25.0) vs 10.0 (7.0, 14.8), median (25th-75th percentile); p = 0.17), and ventilator-free days at day 28 (14.0 (2.0, 23.0) vs 19.0 (0.0, 24.0), p = 0.55) between the two groups. The incidence of new barotrauma was zero. Compared with control group, significantly lower ΔD1-SOFA and ΔD2-SOFA were found in the EIT group (p < 0.001) in a post hoc comparison. Moreover, the EIT group exhibited a significant decrease of SOFA at day 2 compared with baseline (paired t-test, difference by - 1 (- 3.5, 0), p = 0.001). However, the control group did show a similar decrease (difference by 1 (- 2, 2), p = 0.131). CONCLUSION: Our study showed a 6% absolute decrease in mortality in the EIT group: a statistically non-significant, but clinically non-negligible result. This result along with the showed improvement in organ function might justify further reserach to validate the beneficial effect of individualized EIT-guided PEEP setting on clinical outcomes of patients with ARDS. TRIAL REGISTRATION: ClinicalTrials, NCT02361398. Registered 11 February 2015-prospectively registered, https://clinicaltrials.gov/show/NCT02361398 .

Neonatal resuscitation: EN-BIRTH multi-country validation study.

BACKGROUND: Annually, 14 million newborns require stimulation to initiate breathing at birth and 6 million require bag-mask-ventilation (BMV). Many countries have invested in facility-based neonatal resuscitation equipment and training. However, there is no consistent tracking for neonatal resuscitation coverage. METHODS: The EN-BIRTH study, in five hospitals in Bangladesh, Nepal, and Tanzania (2017-2018), collected time-stamped data for care around birth, including neonatal resuscitation. Researchers surveyed women and extracted data from routine labour ward registers. To assess accuracy, we compared gold standard observed coverage to survey-reported and register-recorded coverage, using absolute difference, validity ratios, and individual-level validation metrics (sensitivity, specificity, percent agreement). We analysed two resuscitation numerators (stimulation, BMV) and three denominators (live births and fresh stillbirths, non-crying, non-breathing). We also examined timeliness of BMV. Qualitative data were collected from health workers and data collectors regarding barriers and enablers to routine recording of resuscitation. RESULTS: Among 22,752 observed births, 5330 (23.4%) babies did not cry and 3860 (17.0%) did not breathe in the first minute after birth. 16.2% (n = 3688) of babies were stimulated and 4.4% (n = 998) received BMV. Survey-report underestimated coverage of stimulation and BMV. Four of five labour ward registers captured resuscitation numerators. Stimulation had variable accuracy (sensitivity 7.5-40.8%, specificity 66.8-99.5%), BMV accuracy was higher (sensitivity 12.4-48.4%, specificity > 93%), with small absolute differences between observed and recorded BMV. Accuracy did not vary by denominator option. < 1% of BMV was initiated within 1 min of birth. Enablers to register recording included training and data use while barriers included register design, documentation burden, and time pressure. CONCLUSIONS: Population-based surveys are unlikely to be useful for measuring resuscitation coverage given low validity of exit-survey report. Routine labour ward registers have potential to accurately capture BMV as the numerator. Measuring the true denominator for clinical need is complex; newborns may require BMV if breathing ineffectively or experiencing apnoea after initial drying/stimulation or subsequently at any time. Further denominator research is required to evaluate non-crying as a potential alternative in the context of respectful care. Measuring quality gaps, notably timely provision of resuscitation, is crucial for programme improvement and impact, but unlikely to be feasible in routine systems, requiring audits and special studies.

Neurally Adjusted Ventilatory Assist versus Pressure Support Ventilation in Difficult Weaning: A Randomized Trial.

BACKGROUND: Difficult weaning frequently develops in ventilated patients and is associated with poor outcome. In neurally adjusted ventilatory assist, the ventilator is controlled by diaphragm electrical activity, which has been shown to improve patient-ventilator interaction. The objective of this study was to compare neurally adjusted ventilatory assist and pressure support ventilation in patients difficult to wean from mechanical ventilation. METHODS: In this nonblinded randomized clinical trial, difficult-to-wean patients (n = 99) were randomly assigned to neurally adjusted ventilatory assist or pressure support ventilation mode. The primary outcome was the duration of weaning. Secondary outcomes included the proportion of successful weaning, patient-ventilator asynchrony, ventilator-free days, and mortality. Weaning duration was calculated as 28 days for patients under mechanical ventilation at day 28 or deceased before day 28 without successful weaning. RESULTS: Weaning duration in all patients was statistically significant shorter in the neurally adjusted ventilatory assist group (n = 47) compared with the pressure support ventilation group (n = 52; 3.0 [1.2 to 8.0] days vs. 7.4 [2.0 to 28.0], mean difference: -5.5 [95% CI, -9.2 to -1.4], P = 0.039). Post hoc sensitivity analysis also showed that the neurally adjusted ventilatory assist group had shorter weaning duration (hazard ratio, 0.58; 95% CI, 0.34 to 0.98). The proportion of patients with successful weaning from invasive mechanical ventilation was higher in neurally adjusted ventilatory assist (33 of 47 patients, 70%) compared with pressure support ventilation (25 of 52 patients, 48%; respiratory rate for neurally adjusted ventilatory assist: 1.46 [95% CI, 1.04 to 2.05], P = 0.026). The number of ventilator-free days at days 14 and 28 was statistically significantly higher in neurally adjusted ventilatory assist compared with pressure support ventilation. Neurally adjusted ventilatory assist improved patient ventilator interaction. Mortality and length of stay in the intensive care unit and in the hospital were similar among groups. CONCLUSIONS: In patients difficult to wean, neurally adjusted ventilatory assist decreased the duration of weaning and increased ventilator-free days.

Airway pressure morphology and respiratory muscle activity during end-inspiratory occlusions in pressure support ventilation.

BACKGROUND: The driving pressure of the respiratory system is a valuable indicator of global lung stress during passive mechanical ventilation. Monitoring lung stress in assisted ventilation is indispensable, but achieving passive conditions in spontaneously breathing patients to measure driving pressure is challenging. The accuracy of the morphology of airway pressure (Paw) during end-inspiratory occlusion to assure passive conditions during pressure support ventilation has not been examined. METHODS: Retrospective analysis of end-inspiratory occlusions obtained from critically ill patients during pressure support ventilation. Flow, airway, esophageal, gastric, and transdiaphragmatic pressures were analyzed. The rise of gastric pressure during occlusion with a constant/decreasing transdiaphragmatic pressure was used to identify and quantify the expiratory muscle activity. The Paw during occlusion was classified in three patterns, based on the differences at three pre-defined points after occlusion (0.3, 1, and 2 s): a "passive-like" decrease followed by plateau, a pattern with "clear plateau," and an "irregular rise" pattern, which included all cases of late or continuous increase, with or without plateau. RESULTS: Data from 40 patients and 227 occlusions were analyzed. Expiratory muscle activity during occlusion was identified in 79% of occlusions, and at all levels of assist. After classifying occlusions according to Paw pattern, expiratory muscle activity was identified in 52%, 67%, and 100% of cases of Paw of passive-like, clear plateau, or irregular rise pattern, respectively. The driving pressure was evaluated in the 133 occlusions having a passive-like or clear plateau pattern in Paw. An increase in gastric pressure was present in 46%, 62%, and 64% of cases at 0.3, 1, and 2 s, respectively, and it was greater than 2 cmH2O, in 10%, 20%, and 15% of cases at 0.3, 1, and 2 s, respectively. CONCLUSIONS: The pattern of Paw during an end-inspiratory occlusion in pressure support cannot assure the absence of expiratory muscle activity and accurate measurement of driving pressure. Yet, because driving pressure can only be overestimated due to expiratory muscle contraction, in everyday practice, a low driving pressure indicates an absence of global lung over-stretch. A measurement of high driving pressure should prompt further diagnostic workup, such as a measurement of esophageal pressure.

Individualized flow-controlled ventilation compared to best clinical practice pressure-controlled ventilation: a prospective randomized porcine study.

BACKGROUND: Flow-controlled ventilation is a novel ventilation method which allows to individualize ventilation according to dynamic lung mechanic limits based on direct tracheal pressure measurement at a stable constant gas flow during inspiration and expiration. The aim of this porcine study was to compare individualized flow-controlled ventilation (FCV) and current guideline-conform pressure-controlled ventilation (PCV) in long-term ventilation. METHODS: Anesthetized pigs were ventilated with either FCV or PCV over a period of 10 h with a fixed FiO2 of 0.3. FCV settings were individualized by compliance-guided positive end-expiratory pressure (PEEP) and peak pressure (Ppeak) titration. Flow was adjusted to maintain normocapnia and the inspiration to expiration ratio (I:E ratio) was set at 1:1. PCV was performed with a PEEP of 5 cm H2O and Ppeak was set to achieve a tidal volume (VT) of 7 ml/kg. The respiratory rate was adjusted to maintain normocapnia and the I:E ratio was set at 1:1.5. Repeated measurements during observation period were assessed by linear mixed-effects model. RESULTS: In FCV (n = 6), respiratory minute volume was significantly reduced (6.0 vs 12.7, MD - 6.8 (- 8.2 to - 5.4) l/min; p < 0.001) as compared to PCV (n = 6). Oxygenation was improved in the FCV group (paO2 119.8 vs 96.6, MD 23.2 (9.0 to 37.5) Torr; 15.97 vs 12.87, MD 3.10 (1.19 to 5.00) kPa; p = 0.010) and CO2 removal was more efficient (paCO2 40.1 vs 44.9, MD - 4.7 (- 7.4 to - 2.0) Torr; 5.35 vs 5.98, MD - 0.63 (- 0.99 to - 0.27) kPa; p = 0.006). Ppeak and driving pressure were comparable in both groups, whereas PEEP was significantly lower in FCV (p = 0.002). Computed tomography revealed a significant reduction in non-aerated lung tissue in individualized FCV (p = 0.026) and no significant difference in overdistended lung tissue, although a significantly higher VT was applied (8.2 vs 7.6, MD 0.7 (0.2 to 1.2) ml/kg; p = 0.025). CONCLUSION: Our long-term ventilation study demonstrates the applicability of a compliance-guided individualization of FCV settings, which resulted in significantly improved gas exchange and lung tissue aeration without signs of overinflation as compared to best clinical practice PCV.

Proportional assist ventilation versus pressure support ventilation for weaning from mechanical ventilation in adults: a meta-analysis and trial sequential analysis.

BACKGROUND: Pressure support ventilation (PSV) is the prevalent weaning method. Proportional assist ventilation (PAV) is an assisted ventilation mode, which is recently being applied to wean the patients from mechanical ventilation. Whether PAV or PSV is superior for weaning remains unclear. METHODS: Eligible randomized controlled trials published before April 2020 were retrieved from databases. We calculated the risk ratio (RR) and mean difference (MD) with 95% confidence intervals (CIs). RESULTS: Seven articles, involving 634 patients, met the selection criteria. Compared to PSV, PAV was associated with a significantly higher rate of weaning success (fixed-effect RR 1.16; 95% CI 1.07-1.26; I2 = 0.0%; trial sequential analysis-adjusted CI 1.03-1.30), and the trial sequential monitoring boundary for benefit was crossed. Compared to PSV, PAV was associated with a lower proportion of patients requiring reintubation (RR 0.49; 95% CI 0.28-0.87; I2 = 0%), a shorter ICU length of stay (MD - 1.58 (days), 95% CI - 2.68 to - 0.47; I2 = 0%), and a shorter mechanical ventilation duration (MD - 40.26 (hours); 95% CI - 66.67 to - 13.84; I2 = 0%). There was no significant difference between PAV and PSV with regard to mortality (RR 0.66; 95% CI 0.42-1.06; I2 = 0%) or weaning duration (MD - 0.01 (hours); 95% CI - 1.30-1.28; I2 = 0%). CONCLUSION: The results of the meta-analysis suggest that PAV is superior to PSV in terms of weaning success, and the statistical power is confirmed using trial sequential analysis.

Evidence Supporting Clinical Use of Proportional Assist Ventilation: A Systematic Review and Meta-Analysis of Clinical Trials.

BACKGROUND: While proportional assist ventilation (PAV), generates pressure in proportion to effort without a preselected target, proportional assist ventilation plus (PAV+) measures compliance and resistance, calculates work of breathing, and adjusts support to a preset assistance level. OBJECTIVE: To summarize randomized controlled trials (RCTs) comparing invasive or noninvasive PAV or PAV+ in critically ill patients. Data Sources: We searched multiple databases to April 2017 without language restrictions and conference proceedings from 5 meetings to identify randomized parallel-group and crossover RCTs that compared invasive or noninvasive PAV or PAV+ to another mode in critically ill adults or children and reported at least 1 clinically important outcome. RESULTS: We identified 14 RCTs (11 parallel group and 3 crossover) assessing PAV (n = 7) and PAV+ (n = 7) involving 931 adult patients. We found no effect of noninvasive PAV (vs noninvasive pressure support [PS]) on intubation (risk ratio 0.92 [0.59 to 1.43], I2 = 0%) or invasive PAV (vs invasive PS) on percentage rapid eye movement sleep (mean difference [MD] -2.93% [-14.20 to ±8.34], I2 = 43%). Compared to invasive PS, invasive PAV+ showed a nonsignificant increase in weaning time (MD +0.54 [-0.67 to +1.75] hours, I2 = 0%), but no effect on hospital mortality, reintubation, or tracheostomy. CONCLUSIONS: Current evidence does not support the use of invasive or noninvasive PAV or invasive PAV+ in critically ill adults. Amid low to moderate heterogeneity, we identified 3 promising areas for future research including assessing the role of noninvasive PAV as an initial support strategy in patients with acute respiratory failure, invasive PAV on sleep quality during invasive ventilation, and possibly invasive PAV+ for weaning.

Effect of Endotracheal Tube Size, Respiratory System Mechanics, and Ventilator Settings on Driving Pressure.

OBJECTIVES: We sought to investigate factors that affect the difference between the peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions (resistive pressure) during pressure controlled ventilation across a range of endotracheal tube sizes, respiratory mechanics, and ventilator settings. DESIGN: In vitro study. SETTING: Research laboratory. PATIENTS: None. INTERVENTIONS: An in vitro bench model of the intubated respiratory system during pressure controlled ventilation was used to obtain the difference between peak inspiratory pressure measured at the Y-piece under dynamic flow conditions and plateau pressure measured under zero-flow conditions across a range of endotracheal tubes sizes (3.0-8.0 mm). Measurements were taken at combinations of pressure above positive end-expiratory pressure (10, 15, and 20 cm H2O), airway resistance (no, low, high), respiratory system compliance (ranging from normal to extremely severe), and inspiratory time at constant positive end-expiratory pressure (5 cm H2O). Multiple regression analysis was used to construct models predicting resistive pressure stratified by endotracheal tube size. MEASUREMENTS AND MAIN RESULTS: On univariate regression analysis, respiratory system compliance (ß -1.5; 95% CI, -1.7 to -1.4; p < 0.001), respiratory system resistance (ß 1.7; 95% CI, 1.5-2.0; p < 0.001), pressure above positive end-expiratory pressure (ß 1.7; 95% CI, 1.4-2.0; p < 0.001), and inspiratory time (ß -0.7; 95% CI, -1.0 to -0.4; p < 0.001) were associated with resistive pressure. Multiple linear regression analysis showed the independent association between increasing respiratory system compliance, increasing airway resistance, increasing pressure above positive end-expiratory pressure, and decreasing inspiratory time and resistive pressure across all endotracheal tube sizes. Inspiratory time was the strongest variable associated with a proportional increase in resistive pressure. The contribution of airway resistance became more prominent with increasing endotracheal tube size. CONCLUSIONS: Peak inspiratory pressures measured during pressure controlled ventilation overestimated plateau pressure irrespective of endotracheal tube size, especially with decreased inspiratory time or increased airway resistance.

Assessment of dynamic changes in cardiac function during resuscitation of patients with suspected septic shock: A prospective, observational, cohort study.

STUDY OBJECTIVE: To describe changes in cardiac function throughout the course of resuscitation of patients with suspected septic shock. METHODS: Prospective observational cohort study of Point-of-Care Transthoracic Echocardiograms (TTE) obtained in Emergency Department (ED) patients with a presumed infectious cause of hypotension within one hour of initiating IV fluid resuscitation. Findings of this pre-resuscitation TTE were compared to mid-resuscitation TTE (obtained upon disposition from the ED), and post-resuscitation TTE (obtained after admission to hospital). RESULTS: 22 enrolled patients had a second TTE available for comparison to the initial, pre-resuscitation TTE. 12 patients had a mid-resuscitation TTE and 16 patients had a post-resuscitation TTE. We observed a high incidence of changes on TTE during the clinical course of resuscitation (14/22 [64%]). Patients who developed LV or RV dysfunction during resuscitation were more likely to require vasopressor infusion and ICU admission (Spearman's coefficients [95% CI] of 0.68 [0.36-0.86] and 0.47 [0.04;0.75] respectively). Development of RV dysfunction alone was associated with increased use of positive pressure ventilation and vasopressor infusion (Spearman's coefficients [95% CI] of 0.43 [0;0.72] and 0.47 [0.05,0.75] respectively). CONCLUSIONS: Cardiac function changes assessed by TTE are common during the resuscitation of patients with septic shock. These changes likely reflect the underlying physiology of patients with septic shock and correlate with need for interventions and higher level of care. Further work is required to characterize these changes and to elucidate how to use these physiologic data to guide management.

Impact of Anesthetic and Ventilation Strategies on Invasive Hemodynamic Measurements in Pediatric Heart Transplant Recipients.

BACKGROUND: Care of pediatric heart transplant recipients relies upon serial invasive hemodynamic evaluation, generally performed under the artificial conditions created by anesthesia and supportive ventilation. OBJECTIVES: This study aimed to evaluate the hemodynamic impacts of different anesthetic and ventilatory strategies. METHODS: We compared retrospectively the cardiac index, right- and left-sided filling pressures, and pulmonary and systemic vascular resistances of all clinically well and rejection-free heart transplant recipients catheterized from 2005 through 2017. Effects of spontaneous versus positive pressure ventilation and of sedation versus general anesthesia were tested with generalized linear mixed models for repeated measures using robust sandwich estimators of the covariance matrices. Least squared means showed adjusted mean outcome values, controlled for appropriate confounders. RESULTS: 720 catheterizations from 101 recipients met inclusion criteria. Adjusted cardiac index was 3.14 L/min/m2 (95% CI 3.01-3.67) among spontaneously breathing and 2.71 L/min/m2 (95% CI 2.56-2.86) among ventilated recipients (p < 0.0001). With spontaneous breathing, left filling pressures were lower (9.9 vs 11.0 mmHg, p = 0.030) and systemic vascular resistances were higher (24.0 vs 20.5 Woods units, p < 0.0001). After isolating sedated from anesthetized spontaneously breathing patients, the observed differences in filling pressures and resistances emerged as a function of sedation versus general anesthesia rather than of spontaneous versus positive pressure ventilation. CONCLUSION: In pediatric heart transplant recipients, positive pressure ventilation reduces cardiac output but does not alter filling pressures or vascular resistances. Moderate sedation yields lower left filling pressures and higher systemic vascular resistances than does general anesthesia. Differences are quantitatively small.

ResUHUrge: A Low Cost and Fully Functional Ventilator Indicated for Application in COVID-19 Patients.

Although the cure for the SARS-CoV-2 virus (COVID-19) will come in the form of pharmaceutical solutions and/or a vaccine, one of the only ways to face it at present is to guarantee the best quality of health for patients, so that they can overcome the disease on their own. Therefore, and considering that COVID-19 generally causes damage to the respiratory system (in the form of lung infection), it is essential to ensure the best pulmonary ventilation for the patient. However, depending on the severity of the disease and the health condition of the patient, the situation can become critical when the patient has respiratory distress or becomes unable to breathe on his/her own. In that case, the ventilator becomes the lifeline of the patient. This device must keep patients stable until, on their own or with the help of medications, they manage to overcome the lung infection. However, with thousands or hundreds of thousands of infected patients, no country has enough ventilators. If this situation has become critical in the Global North, it has turned disastrous in developing countries, where ventilators are even more scarce. This article shows the race against time of a multidisciplinary research team at the University of Huelva, UHU, southwest of Spain, to develop an inexpensive, multifunctional, and easy-to-manufacture ventilator, which has been named ResUHUrge. The device meets all medical requirements and is developed with open-source hardware and software.

Baseline Characteristics and Outcomes of 1591 Patients Infected With SARS-CoV-2 Admitted to ICUs of the Lombardy Region, Italy.

Importance: In December 2019, a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) emerged in China and has spread globally, creating a pandemic. Information about the clinical characteristics of infected patients who require intensive care is limited. Objective: To characterize patients with coronavirus disease 2019 (COVID-19) requiring treatment in an intensive care unit (ICU) in the Lombardy region of Italy. Design, Setting, and Participants: Retrospective case series of 1591 consecutive patients with laboratory-confirmed COVID-19 referred for ICU admission to the coordinator center (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy) of the COVID-19 Lombardy ICU Network and treated at one of the ICUs of the 72 hospitals in this network between February 20 and March 18, 2020. Date of final follow-up was March 25, 2020. Exposures: SARS-CoV-2 infection confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Main Outcomes and Measures: Demographic and clinical data were collected, including data on clinical management, respiratory failure, and patient mortality. Data were recorded by the coordinator center on an electronic worksheet during telephone calls by the staff of the COVID-19 Lombardy ICU Network. Results: Of the 1591 patients included in the study, the median (IQR) age was 63 (56-70) years and 1304 (82%) were male. Of the 1043 patients with available data, 709 (68%) had at least 1 comorbidity and 509 (49%) had hypertension. Among 1300 patients with available respiratory support data, 1287 (99% [95% CI, 98%-99%]) needed respiratory support, including 1150 (88% [95% CI, 87%-90%]) who received mechanical ventilation and 137 (11% [95% CI, 9%-12%]) who received noninvasive ventilation. The median positive end-expiratory pressure (PEEP) was 14 (IQR, 12-16) cm H2O, and Fio2 was greater than 50% in 89% of patients. The median Pao2/Fio2 was 160 (IQR, 114-220). The median PEEP level was not different between younger patients (n = 503 aged ≤63 years) and older patients (n = 514 aged ≥64 years) (14 [IQR, 12-15] vs 14 [IQR, 12-16] cm H2O, respectively; median difference, 0 [95% CI, 0-0]; P = .94). Median Fio2 was lower in younger patients: 60% (IQR, 50%-80%) vs 70% (IQR, 50%-80%) (median difference, -10% [95% CI, -14% to 6%]; P = .006), and median Pao2/Fio2 was higher in younger patients: 163.5 (IQR, 120-230) vs 156 (IQR, 110-205) (median difference, 7 [95% CI, -8 to 22]; P = .02). Patients with hypertension (n = 509) were older than those without hypertension (n = 526) (median [IQR] age, 66 years [60-72] vs 62 years [54-68]; P < .001) and had lower Pao2/Fio2 (median [IQR], 146 [105-214] vs 173 [120-222]; median difference, -27 [95% CI, -42 to -12]; P = .005). Among the 1581 patients with ICU disposition data available as of March 25, 2020, 920 patients (58% [95% CI, 56%-61%]) were still in the ICU, 256 (16% [95% CI, 14%-18%]) were discharged from the ICU, and 405 (26% [95% CI, 23%-28%]) had died in the ICU. Older patients (n = 786; age ≥64 years) had higher mortality than younger patients (n = 795; age ≤63 years) (36% vs 15%; difference, 21% [95% CI, 17%-26%]; P < .001). Conclusions and Relevance: In this case series of critically ill patients with laboratory-confirmed COVID-19 admitted to ICUs in Lombardy, Italy, the majority were older men, a large proportion required mechanical ventilation and high levels of PEEP, and ICU mortality was 26%.

Early Identification of Acute Respiratory Distress Syndrome in the Absence of Positive Pressure Ventilation: Implications for Revision of the Berlin Criteria for Acute Respiratory Distress Syndrome.

OBJECTIVES: To assess whether patients breathing spontaneously under standard oxygen could be recognized early as acute respiratory distress syndrome patients according to the current Berlin definition. DESIGN: A post hoc analysis from two prospective studies. SETTING: Twenty-three French ICUs. PATIENTS: All patients admitted for acute hypoxemic respiratory failure and treated with noninvasive ventilation were analyzed. Patients with cardiogenic pulmonary edema, acute exacerbation of chronic obstructive pulmonary disease, or hypercapnia were excluded. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The PaO2/FIO2 ratio was estimated at admission under standard oxygen and then under noninvasive ventilation 1 hour after initiation and within the first 24 hours. Among the 219 patients treated with noninvasive ventilation for acute hypoxemic respiratory failure, 180 (82%) had bilateral infiltrates including 161 patients with PaO2/FIO2 less than or equal to 300 mm Hg under standard oxygen. Among them, 127 were treated with positive end-expiratory pressure of at least 5 cm H2O, and 120 (94%) fulfilled criteria for acute respiratory distress syndrome within the first 24 hours. The mortality rate of patients with bilateral infiltrates and PaO2/FIO2 less than or equal to 300 mm Hg under standard oxygen was 29%, a rate very close to that of intubated patients with acute respiratory distress syndrome in the Berlin definition. CONCLUSIONS: Almost all patients with pulmonary bilateral infiltrates and a PaO2/FIO2 less than or equal to 300 mm Hg under standard oxygen fulfilled the acute respiratory distress syndrome criteria under noninvasive ventilation within the first 24 hours. Their mortality rate was similar to that reported in the Berlin definition of acute respiratory distress syndrome. Therefore, spontaneous breathing patients with the acute respiratory distress syndrome criteria could be identified early without positive pressure ventilation.

Does Providing Positive Airway Pressure for Sleep Apnea Change Health Care Utilization?

BACKGROUND: Sleep apnea is underdiagnosed and thus undertreated. If therapy for sleep apnea results in reduced health care utilization in an entire treated population, then decision-makers will have key information for allocating limited health care resources. OBJECTIVES: To determine whether positive airway pressure (PAP) for sleep apnea was associated with reduced health care utilization in an entire treated population. RESEARCH DESIGN: This was a retrospective cohort; propensity score-matched cases and noncases; pre-post analyses of individual subject utilization. SUBJECTS: Electronic health records were used to identify adult subjects diagnosed with sleep apnea and dispensed PAP therapy (cases) and those without either diagnosed sleep apnea or dispensed PAP therapy (noncases). MEASURES: Acute care hospital days and dispensed medication days supply were compared in cases and noncases. Negative binomial regression was used to model utilization for up to 5 years before and 7 years after PAP dispensation (cases) or a random date (noncases). The association of PAP with changing annual utilization was estimated. RESULTS: There were 13,271 cases and 13,271 matched noncases from 2008 to 2012 for analyses. Trends in the annual rate of acute care utilization were no different between cases and noncases (rate ratio, 0.98, P=0.543). Trends in the annual rate of medication utilization were no different between cases and noncases (rate ratio, 1.008, P=0.112). CONCLUSIONS: PAP dispensation for sleep apnea did not appear to reduce the rate of acute care and medication utilization over several years of follow-up in a large integrated health care system.

Best PEEP trials are dependent on tidal volume.

Determining the optimal positive end-expiratory pressure (PEEP) in patients with acute respiratory distress syndrome remains an area of active investigation. Most trials individualizing PEEP optimize one physiologic parameter (e.g., driving pressure) by titrating PEEP while holding other ventilator settings constant. Optimal PEEP, however, may depend on the tidal volume, and changing the tidal volume with which a best PEEP trial is performed may lead to different best PEEP settings in the same patient. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02871102. Registered on 12 August 2016.

Feasibility and safety of low-flow extracorporeal CO2 removal managed with a renal replacement platform to enhance lung-protective ventilation of patients with mild-to-moderate ARDS.

BACKGROUND: Extracorporeal carbon-dioxide removal (ECCO2R) might allow ultraprotective mechanical ventilation with lower tidal volume (VT) (< 6 ml/kg predicted body weight), plateau pressure (Pplat) (< 30 cmH2O), and driving pressure to limit ventilator-induced lung injury. This study was undertaken to assess the feasibility and safety of ECCO2R managed with a renal replacement therapy (RRT) platform to enable very low tidal volume ventilation of patients with mild-to-moderate acute respiratory distress syndrome (ARDS). METHODS: Twenty patients with mild (n = 8) or moderate (n = 12) ARDS were included. VT was gradually lowered from 6 to 5, 4.5, and 4 ml/kg, and PEEP adjusted to reach 23 ≤ Pplat ≤ 25 cmH2O. Standalone ECCO2R (no hemofilter associated with the RRT platform) was initiated when arterial PaCO2 increased by > 20% from its initial value. Ventilation parameters (VT, respiratory rate, PEEP), respiratory system compliance, Pplat and driving pressure, arterial blood gases, and ECCO2R-system operational characteristics were collected during at least 24 h of very low tidal volume ventilation. Complications, day-28 mortality, need for adjuvant therapies, and data on weaning off ECCO2R and mechanical ventilation were also recorded. RESULTS: While VT was reduced from 6 to 4 ml/kg and Pplat kept < 25 cmH2O, PEEP was significantly increased from 13.4 ± 3.6 cmH2O at baseline to 15.0 ± 3.4 cmH2O, and the driving pressure was significantly reduced from 13.0 ± 4.8 to 7.9 ± 3.2 cmH2O (both p < 0.05). The PaO2/FiO2 ratio and respiratory-system compliance were not modified after VT reduction. Mild respiratory acidosis occurred, with mean PaCO2 increasing from 43 ± 8 to 53 ± 9 mmHg and mean pH decreasing from 7.39 ± 0.1 to 7.32 ± 0.10 from baseline to 4 ml/kg VT, while the respiratory rate was not altered. Mean extracorporeal blood flow, sweep-gas flow, and CO2 removal were 421 ± 40 ml/min, 10 ± 0.3 L/min, and 51 ± 26 ml/min, respectively. Mean treatment duration was 31 ± 22 h. Day-28 mortality was 15%. CONCLUSIONS: A low-flow ECCO2R device managed with an RRT platform easily and safely enabled very low tidal volume ventilation with moderate increase in PaCO2 in patients with mild-to-moderate ARDS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02606240. Registered on 17 November 2015.

[Stepwise Diagnostics, Federal Joint Committee Directive and Actual Care in the Case of Sleep-related Breathing Disorders - An Analysis Based on Claims Data of the Techniker Krankenkasse]. / Stufendiagnostik nach der Richtlinie des G-BA und Versorgungswirklichkeit bei vermuteter Schlafapnoe ­ eine Analyse basierend auf Routinedaten der Techniker Krankenkasse.

In 2004, the Federal Joint Committee (G-BA) published a new directive for examination and treatment methods with respect to sleep-related breathing disorders for SHI-accredited physicians. The examination procedure is classified in four steps: anamnesis, clinical assessment, cardiorespiratory polygraphy (PG) and cardiorespiratory polysomnography (PSG). Starting with the date of the first PSG we analysed 1. whether this examination was preceded by a polygraphy, 2. whether there was a gain of diagnostic information through PSG, and 3. whether a PSG was used for the first adjustment examinations and controls after prescription of a positive airway pressure device. The analysis is based on claims data from the Techniker Krankenkasse (2009-2012). Diagnostic services were identified by fee schedule codes (EBM) for outpatient services and by procedure codes (OPS) for inpatient services. Sleep disorders were operationalised by ICD-10 codes and information was completed by prescriptions of a CPAP equipment.The study is based on data from 6.6 million persons who were permanently insured from 01.01.2009 to 30.06.2012 by TK. A preceding PG 90 (180) days before PSG was found for less than 56% (73%) of the analysed insured persons. By the latter procedure, only about 60% of the cases with no clear diagnostic information (G47.39) in the preceding quarter could be specified. Prescription of a positive airway pressure device within 90 days after PSG was found for about 45% of the insured. Concerning the stepwise diagnostic procedure for sleep disorders for SHI-accredited physicians, the directive was followed only partly. Against the background of an evidence-based, effective, and efficient diagnostic approach, the results show a clear need for action.