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Introduction Experimental work provides insight into potential lung protective strategies. The objective of this study was to evaluate markers of ventilator-induced lung injury after two different ventilation approaches: (1) a "conventional" lung-protective strategy (volume control (VC) with low tidal volume, positive end-expiratory pressure (PEEP) and paralysis), (2) a physiological approach with spontaneous breathing, permitting synchrony, variability and a liberated airway. For this, we used non-invasive Neurally Adjusted Ventilatory Assist (NIVNAVA), with the hypothesis that liberation of upper airways and the ventilator's integration with lung protective reflexes would be equally lung protective. Methods In this controlled and randomized in vivo laboratory study, 25 adult White New Zealand rabbits were studied. There were five non-ventilated control animals. There were 20 with HCl aspiration-induced studied, including five non-ventilated control animals. Twenty animals with aspiration-induced lung injury were randomized lung injury and they were randomized to ventilation with either VC (6 mL/kg, PEEP 5 cmH2O, and paralysis) or NIV-NAVA for six hours (PEEP = zero because of leaks). Markers of lung function, lung injury, vital signs and ventilator parameters were assessed. Results At the end of six hours of ventilation (n = 20), there were no significant differences between VC and NIV-NAVA for vital signs, PaO2/FiO2 ratio, lung wet-to-dry ratio and brochoalveolar Interleukin 8 (Il-8). Plasma IL-8 was higher in VC (P <0.05). Lung injury score was lower for NIV-NAVA (P = 0.03). Dynamic lung compliance recovered after six hours in NIV-NAVA but not in VC (P <0.05). During VC, peak pressures increased from 9.2 ± 2.4 cm H2O (hour 1) to 12.3 ± 12.3 cm H2O (hour 6) (P <0.05). During NIV-NAVA, the tracheal end-expiratory pressure was similar to the end-expiratory pressure during VC. Two animals regurgitated during NIV-NAVA, without clinical consequences, and survived the protocol. Conclusions In experimental acute lung injury, NIV-NAVA is as lung-protective as VC 6 ml/kg with PEEP. [ABSTRACT FROM AUTHOR]

Introduction: Based on the hypothesis that failure of weaning from mechanical ventilation is caused by respiratory demand exceeding the capacity of the respiratory muscles, we evaluated whether extubation failure could be characterized by increased respiratory drive and impaired efficiency to generate inspiratory pressure and ventilation .Methods: Airway pressure, flow, volume, breathing frequency, and diaphragm electrical activity were measured in a heterogeneous group of patients deemed ready for a spontaneous breathing trial. Efficiency to convert neuromuscular activity into inspiratory pressure was calculated as the ratio of negative airway pressure and diaphragm electrical activity during an inspiratory occlusion. Efficiency to convert neuromuscular activity into volume was calculated as the ratio of the tidal volume to diaphragm electrical activity. All variables were obtained during a 30-minute spontaneous breathing trial on continuous positive airway pressure (CPAP) of 5 cm H2O and compared between patients for whom extubation succeeded with those for whom either the spontaneous breathing trial failed or for those who passed, but then the extubation failed. Results: Of 52 patients enrolled in the study, 35 (67.3%) were successfully extubated, and 17 (32.7%) were not. Patients for whom it failed had higher diaphragm electrical activity (48%; P < 0.001) and a lower efficiency to convert neuromuscular activity into inspiratory pressure and tidal volume (40% (P < 0.001) and 53% (P < 0.001)), respectively. Neuroventilatory efficiency demonstrated the greatest predictability for weaning success. Conclusions: This study shows that a mixed group of critically ill patients for whom weaning fails have increased neural respiratory drive and impaired ability to convert neuromuscular activity into tidal ventilation, in part because of diaphragm weakness. Trial Registration: Clinicaltrials.gov identifier NCT01065428. ©2012 Liu et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. [ABSTRACT FROM AUTHOR]

Background: Neurally adjusted ventilatory assist (NAVA) is a pneumatically-independent mode of mechanical ventilation controlled by diaphragm electrical activity (EAdi), and has not yet been implemented in very small species. Objectives: The aims of the study were to evaluate the feasibility of applying NAVA in very small species and to compare this to pressure support ventilation (PSV) in terms of ventilatory efficiency and breathing pattern, and evaluate the impact of instrumental dead space on breathing pattern during both modes. Methods: Nine healthy rats (mean weight 385 8 4 g) were studied while breathing on PSV or NAVA, at baseline or with added dead space. Results: A clear difference in breathing pattern between NAVA and PSV was observed during both baseline and dead space, where PSV – despite similar EAdi and tidal volume as during NAVA – caused shortened inspiratory time (p < 0.05) and increased the respiratory rate (p < 0.05). A higher minute ventilation (p < 0.05) in order to reach the same arterial CO2 was observed. Ineffective inspiratory efforts occurred only during PSV and decreased with the dead space. Conclusion: This study demonstrates, in a small group of animals, that NAVA can deliver assist in very small species with a higher efficiency than PSV in terms of eliminating CO2 for a given minute ventilation. [ABSTRACT FROM AUTHOR]

Neurally adjusted ventilatory assist uses the electrical activity of the diaphragm (EAdi)—a pneumatically-independent signal—to control the timing and pressure of the ventilation delivered, and should not be affected by leaks. The aim of this study was to evaluate whether NAVA can deliver assist in synchrony and proportionally to EAdi after extubation, with a leaky non-invasive interface. Prospective, controlled experimental study in an animal laboratory. Ten rabbits, anesthetized, mechanically ventilated. Following lung injury, the following was performed in sequential order: (1) NAVA delivered via oral endotracheal tube with PEEP; (2) same as (1) without PEEP; (3) non-invasive NAVA at unchanged NAVA level and no PEEP via a single nasal prong; (4) no assist; (5) non-invasive NAVA at progressively increasing NAVA levels. EAdi, esophageal pressure, blood gases and hemodynamics were measured during each condition. For the same NAVA level, the mean delivered pressure above PEEP increased from 3.9 ± 1.4 cmH2O (intubated) to 7.5 ± 3.8 cmH2O (non-invasive) ( p < 0.05) because of increased EAdi. No changes were observed in PaO2 and PaCO2. Increasing the NAVA level fourfold during non-invasive NAVA restored EAdi and esophageal pressure swings to pre-extubation levels. Triggering (106 ± 20 ms) and cycling-off delays (40 ± 21 ms) during intubation were minimal and not worsened by the leak (95 ± 13 ms and 33 ± 9 ms, respectively). NAVA can be effective in delivering non-invasive ventilation even when the interface with the patient is excessively leaky, and can unload the respiratory muscles while maintaining synchrony with the subject's demand. [ABSTRACT FROM AUTHOR]

Background: We previously showed in animals that transpulmonary driving pressure (PL) can be estimated during Neurally Adjusted Ventilatory Assist (NAVA) and Neural Pressure Support (NPS) using a single lower assist maneuver (LAM). The aim of this study was to test the LAM-based estimate of PL (PL_LAM) in patients with acute respiratory failure. Methods: This was a prospective, physiological, and interventional study in intubated patients with acute respiratory failure. During both NAVA and simulated NPS (high and low levels of assist), a LAM was performed every 3 min by manually reducing the assist to zero for one single breath (by default, ventilator still provides 2 cmH2O). Following NAVA and NPSSIM periods, patients were sedated and passively ventilated in volume control and pressure control ventilation, to obtain PL during controlled mechanical ventilation (PL_CMV). PL using an esophageal balloon (PL_Pes) was also compared to PL_LAM and PL_CMV. We measured diaphragm electrical activity (Edi), ventilator pressure (PVent), esophageal pressure (Pes) and tidal volume. PL_LAM and PL_Pes were compared to themselves, and to PL_CMV for matching flows and volumes. Results: Ten patients were included in the study. For the group, PL_LAM was closely similar to PL_CMV, with a high correlation (R2 = 0.88). Bland–Altman analysis revealed a low Bias of 0.28 cmH2O, and 1.96SD of 5.26 cmH2O. PL_LAM vs PL_Pes were also tightly related (R2 = 0.77). Conclusion: This physiological study in patients confirms our previous pre-clinical data that PL_LAM is as good an estimate as PL_Pes to determine PL, in spontaneously breathing patients on assisted mechanical ventilation. Trial registration The study was registered at clinicaltrials.gov (ID NCT05378802) on November 6, 2021 [ABSTRACT FROM AUTHOR]

Background: Excessive respiratory muscle effort during mechanical ventilation may cause patient self-inflicted lung injury and load-induced diaphragm myotrauma, but there are no non-invasive methods to reliably detect elevated transpulmonary driving pressure and elevated respiratory muscle effort during assisted ventilation. We hypothesized that the swing in airway pressure generated by respiratory muscle effort under assisted ventilation when the airway is briefly occluded (ΔPocc) could be used as a highly feasible non-invasive technique to screen for these conditions.Methods: Respiratory muscle pressure (Pmus), dynamic transpulmonary driving pressure (ΔPL,dyn, the difference between peak and end-expiratory transpulmonary pressure), and ΔPocc were measured daily in mechanically ventilated patients in two ICUs in Toronto, Canada. A conversion factor to predict ΔPL,dyn and Pmus from ΔPocc was derived and validated using cross-validation. External validity was assessed in an independent cohort (Nanjing, China).Results: Fifty-two daily recordings were collected in 16 patients. In this sample, Pmus and ΔPL were frequently excessively high: Pmus exceeded 10 cm H2O on 84% of study days and ΔPL,dyn exceeded 15 cm H2O on 53% of study days. ΔPocc measurements accurately detected Pmus > 10 cm H2O (AUROC 0.92, 95% CI 0.83-0.97) and ΔPL,dyn > 15 cm H2O (AUROC 0.93, 95% CI 0.86-0.99). In the external validation cohort (n = 12), estimating Pmus and ΔPL,dyn from ΔPocc measurements detected excessively high Pmus and ΔPL,dyn with similar accuracy (AUROC ≥ 0.94).Conclusions: Measuring ΔPocc enables accurate non-invasive detection of elevated respiratory muscle pressure and transpulmonary driving pressure. Excessive respiratory effort and transpulmonary driving pressure may be frequent in spontaneously breathing ventilated patients. [ABSTRACT FROM AUTHOR]

Background: Veno-venous extracorporeal CO2 removal (vv-ECCO2R) and non-invasive neurally adjusted ventilator assist (NIV-NAVA) are two promising techniques which may prevent complications related to prolonged invasive mechanical ventilation in patients with acute exacerbation of COPD.Methods: A physiological study of the electrical activity of the diaphragm (Edi) response was conducted with varying degrees of extracorporeal CO2 removal to control the respiratory drive in patients with severe acute exacerbation of COPD breathing on NIV-NAVA.Results: Twenty COPD patients (SAPS II 37 ± 5.6, age 57 ± 9 years) treated with vv-ECCO2R and supported by NIV-NAVA were studied during stepwise weaning of vv-ECCO2R. Based on dyspnea, tolerance, and blood gases, weaning from vv-ECCO2R was successful in 12 and failed in eight patients. Respiratory drive (measured via the Edi) increased to 19 ± 10 μV vs. 56 ± 20 μV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO2 and pH values stable. Edi was the best predictor for vv-ECCO2R weaning failure (ROC analysis AUC 0.95), whereas respiratory rate, rapid shallow breathing index, and tidal volume had lower predictive values. Eventually, 19 patients were discharged home, while one patient died. Mortality at 90 days and 180 days was 15 and 25%, respectively.Conclusions: This study demonstrates for the first time the usefulness of the Edi signal to monitor and guide patients with severe acute exacerbation of COPD on vv-ECCO2R and NIV-NAVA. The Edi during vv-ECCO2R weaning was found to be the best predictor of tolerance to removing vv-ECCO2R. [ABSTRACT FROM AUTHOR]

Background: Diaphragm dysfunction develops frequently in ventilated intensive care unit (ICU) patients. Both disuse atrophy (ventilator over-assist) and high respiratory muscle effort (ventilator under-assist) seem to be involved. A strong rationale exists to monitor diaphragm effort and titrate support to maintain respiratory muscle activity within physiological limits. Diaphragm electromyography is used to quantify breathing effort and has been correlated with transdiaphragmatic pressure and esophageal pressure. The neuromuscular efficiency index (NME) can be used to estimate inspiratory effort, however its repeatability has not been investigated yet. Our goal is to evaluate NME repeatability during an end-expiratory occlusion (NMEoccl) and its use to estimate the pressure generated by the inspiratory muscles (Pmus).Methods: This is a prospective cohort study, performed in a medical-surgical ICU. A total of 31 adult patients were included, all ventilated in neurally adjusted ventilator assist (NAVA) mode with an electrical activity of the diaphragm (EAdi) catheter in situ. At four time points within 72 h five repeated end-expiratory occlusion maneuvers were performed. NMEoccl was calculated by delta airway pressure (ΔPaw)/ΔEAdi and was used to estimate Pmus. The repeatability coefficient (RC) was calculated to investigate the NMEoccl variability.Results: A total number of 459 maneuvers were obtained. At time T = 0 mean NMEoccl was 1.22 ± 0.86 cmH2O/μV with a RC of 82.6%. This implies that when NMEoccl is 1.22 cmH2O/μV, it is expected with a probability of 95% that the subsequent measured NMEoccl will be between 2.22 and 0.22 cmH2O/μV. Additional EAdi waveform analysis to correct for non-physiological appearing waveforms, did not improve NMEoccl variability. Selecting three out of five occlusions with the lowest variability reduced the RC to 29.8%.Conclusions: Repeated measurements of NMEoccl exhibit high variability, limiting the ability of a single NMEoccl maneuver to estimate neuromuscular efficiency and therefore the pressure generated by the inspiratory muscles based on EAdi. [ABSTRACT FROM AUTHOR]

Background: The unsuccessful extubation in patients with traumatic cervical spinal cord injuries (CSCI) may result from impairment diaphragm function and monitoring of diaphragm electrical activity (EAdi) can be informative in guiding extubation. We aimed to evaluate whether the change of EAdi during a single maximal maneuver can predict extubation outcomes in CSCI patients. Methods: This is a retrospective study of CSCI patients requiring mechanical ventilation in the ICU of a tertiary hospital. A single maximal maneuver was performed by asking each patient to inhale with maximum strength during the first spontaneous breathing trial (SBT). The baseline (during SBT before maximal maneuver), maximum (during the single maximal maneuver), and the increase of EAdi (ΔEAdi, equal to the difference between baseline and maximal) were measured. The primary outcome was extubation success, defined as no reintubation after the first extubation and no tracheostomy before any extubation during the ICU stay. Results: Among 107 patients enrolled, 50 (46.7%) were extubated successfully at the first SBT. Baseline EAdi, maximum EAdi, and ΔEAdi were significantly higher, and the rapid shallow breathing index was lower in patients who were extubated successfully than in those who failed. By multivariable logistic analysis, ΔEAdi was independently associated with successful extubation (OR 2.03, 95% CI 1.52–3.17). ΔEAdi demonstrated high diagnostic accuracy in predicting extubation success with an AUROC 0.978 (95% CI 0.941–0.995), and the cut-off value was 7.0 μV. Conclusions: The increase of EAdi from baseline SBT during a single maximal maneuver is associated with successful extubation and can help guide extubation in CSCI patients. [ABSTRACT FROM AUTHOR]

Background: Reverse triggering is a delayed asynchronous contraction of the diaphragm triggered by passive insufflation by the ventilator in sedated mechanically ventilated patients. The incidence of reverse triggering is unknown. This study aimed at determining the incidence of reverse triggering in critically ill patients under controlled ventilation.Methods: In this ancillary study, patients were continuously monitored with a catheter measuring the electrical activity of the diaphragm. A method for automatic detection of reverse triggering using electrical activity of the diaphragm was developed in a derivation sample and validated in a subsequent sample. The authors assessed the predictive value of the software. In 39 recently intubated patients under assist-control ventilation, a 1-h recording obtained 24 h after intubation was used to determine the primary outcome of the study. The authors also compared patients' demographics, sedation depth, ventilation settings, and time to transition to assisted ventilation or extubation according to the median rate of reverse triggering.Results: The positive and negative predictive value of the software for detecting reverse triggering were 0.74 (95% CI, 0.67 to 0.81) and 0.97 (95% CI, 0.96 to 0.98). Using a threshold of 1 μV of electrical activity to define diaphragm activation, median reverse triggering rate was 8% (range, 0.1 to 75), with 44% (17 of 39) of patients having greater than or equal to 10% of breaths with reverse triggering. Using a threshold of 3 μV, 26% (10 of 39) of patients had greater than or equal to 10% reverse triggering. Patients with more reverse triggering were more likely to progress to an assisted mode or extubation within the following 24 h (12 of 39 [68%]) vs. 7 of 20 [35%]; P = 0.039).Conclusions: Reverse triggering detection based on electrical activity of the diaphragm suggests that this asynchrony is highly prevalent at 24 h after intubation under assist-control ventilation. Reverse triggering seems to occur during the transition phase between deep sedation and the onset of patient triggering.Editor’s Perspective: [ABSTRACT FROM AUTHOR]

Background: A high-flow nasal cannula (cHFNC) delivers flow continuously (during inspiration and expiration). Using the diaphragm electrical activity (Edi), synchronizing HFNC could be an alternative (cycling high/low flow on inspiration/expiration, respectively). The objective of this study was to demonstrate the feasibility of synchronized HFNC (sHFNC) and compare it to cHFNC., Methods: Different levels of cHFNC and sHFNC (4, 6, 8, and 10 liters per minute [LPM], with 2 LPM on expiration for sHFNC) were compared in eight rabbits (mean weight 3.16 kg), before and after acute lung injury (pre-ALI and post-ALI). Edi, tracheal pressure (Ptr), esophageal pressure (Pes), flow, and arterial CO 2 were measured. In addition to the animal study, one 3.52 kg infant received sHFNC and cHFNC using a Servo-U ventilator., Results: In the animal study, there were more pronounced decreases in Edi, reduced Pes swings and reduced PaCO 2 at comparable flows during sHFNC compared to cHFNC both pre and post-ALI (p < .05). Baseline (pre-inspiratory) Ptr was 2-7 cmH 2 O greater during cHFNC (p < .05) indicating more dynamic hyperinflation. In one infant, the ventilator performed as expected, delivering Edi-synchronized high/low flow., Conclusion: Synchronizing high flow unloaded breathing, decreased Edi, and reduced PaCO 2 in an animal model and is feasible in infants., (© 2024 Wiley Periodicals LLC.)

Background: Pre-clinical studies suggest that dyssynchronous diaphragm contractions during mechanical ventilation may cause acute diaphragm dysfunction. We aimed to describe the variability in diaphragm contractile loading conditions during mechanical ventilation and to establish whether dyssynchronous diaphragm contractions are associated with the development of impaired diaphragm dysfunction., Methods: In patients receiving invasive mechanical ventilation for pneumonia, septic shock, acute respiratory distress syndrome, or acute brain injury, airway flow and pressure and diaphragm electrical activity (Edi) were recorded hourly around the clock for up to 7 days. Dyssynchronous post-inspiratory diaphragm loading was defined based on the duration of neural inspiration after expiratory cycling of the ventilator. Diaphragm function was assessed on a daily basis by neuromuscular coupling (NMC, the ratio of transdiaphragmatic pressure to diaphragm electrical activity)., Results: A total of 4508 hourly recordings were collected in 45 patients. Edi was low or absent (≤ 5 µV) in 51% of study hours (median 71 h per patient, interquartile range 39-101 h). Dyssynchronous post-inspiratory loading was present in 13% of study hours (median 7 h per patient, interquartile range 2-22 h). The probability of dyssynchronous post-inspiratory loading was increased with reverse triggering (odds ratio 15, 95% CI 8-35) and premature cycling (odds ratio 8, 95% CI 6-10). The duration and magnitude of dyssynchronous post-inspiratory loading were associated with a progressive decline in diaphragm NMC (p < 0.01 for interaction with time)., Conclusions: Dyssynchronous diaphragm contractions may impair diaphragm function during mechanical ventilation., Trial Registration: MYOTRAUMA, ClinicalTrials.gov NCT03108118. Registered 04 April 2017 (retrospectively registered)., (© 2024. The Author(s).)

Objective: To measure tidal volume delivery during nasal intermittent positive pressure ventilation with two nasal interfaces: infant cannula and nasal prongs., Study Design: A single-center crossover study of neonates with mild respiratory distress. Fifteen preterm neonates were randomized to initial interface of infant cannula or nasal prongs and monitored on a sequence of pressure settings first on the initial interface, then repeated on the alternate interface. We compared relative tidal volumes between the two interfaces with two-way repeated measures ANOVA during three breath types: synchronized (I), patient effort without ventilator breaths (II), and ventilator breaths without patient effort (III). Clinical trial #NCT04326270., Results: Type III breaths delivered no significant tidal volume. No significant difference was measured in relative tidal volume delivery between the interfaces when breath types were matched., Conclusions: Nasal intermittent positive pressure ventilation delivers neither clinically nor statistically significant tidal volume with either infant cannula or nasal prongs., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Mechanical ventilation is applied to unload the respiratory muscles, but knowledge about transpulmonary driving pressure (ΔP L ) is important to minimize lung injury. We propose a method to estimate ΔP L during neurally synchronized assisted ventilation, with a simple intervention of lowering the assist for one breath ("lower assist maneuver", LAM)., Methods: In 24 rabbits breathing spontaneously with imposed loads, titrations of increasing assist were performed, with two neurally synchronized modes: neurally adjusted ventilatory assist (NAVA) and neurally triggered pressure support (NPS). Two single LAM breaths (not sequentially, but independently) were performed at each level of assist by acutely setting the assist to zero cm H2O (NPS) or NAVA level 0 cm H2O/uV (NAVA) for one breath. NPS and NAVA titrations were followed by titrations in controlled-modes (volume control, VC and pressure control, PC), under neuro-muscular blockade. Breaths from the NAVA/NPS titrations were matched (for flow and volume) to VC or PC. Throughout all runs, we measured diaphragm electrical activity (Edi) and esophageal pressure (P ES ). We measured ΔP L during the spontaneous modes (P L &#95;P ES ) and controlled mechanical ventilation (CMV) modes (P L &#95; CMV ) with the esophageal balloon. From the LAMs, we derived an estimation of ΔP L ("P L&#95;LAM ") using a correction factor (ratio of volume during the LAM and volume during assist) and compared it to measured ΔP L during passive (VC or PC) and spontaneous breathing (NAVA or NPS). A requirement for the LAM was similar Edi to the assisted breath., Results: All animals successfully underwent titrations and LAMs for NPS/NAVA. One thousand seven-hundred ninety-two (1792) breaths were matched to passive ventilation titrations (matched Vt, r = 0.99). P L&#95;LAM demonstrated strong correlation with P L &#95; CMV (r = 0.83), and P L &#95;P ES (r = 0.77). Bland-Altman analysis revealed little difference between the predicted P L &#95; LAM and measured P L &#95; CMV (Bias = 0.49 cm H2O and 1.96SD = 3.09 cm H2O). For P L &#95;P ES , the bias was 2.2 cm H2O and 1.96SD was 3.4 cm H2O. Analysis of Edi and P ES at peak Edi showed progressively increasing uncoupling with increasing assist., Conclusion: During synchronized mechanical ventilation, a LAM breath allows for estimations of transpulmonary driving pressure, without measuring P ES , and follows a mathematical transfer function to describe respiratory muscle unloading during synchronized assist., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: A sealed abdominal interface was positioned below the diaphragm (the "NeoVest") to apply synchronized and proportional negative pressure ventilation (NPV) and was compared to positive pressure ventilation (PPV) using neurally adjusted ventilatory assist (NAVA). Both modes were controlled by the diaphragm electrical activity (Edi)., Methods: Eleven rabbits (mean weight 2.9 kg) were instrumented, tracheotomized, and ventilated with either NPV or PPV (sequentially) with different loads (resistive, dead space, acute lung injury). Assist with either PPV or NPV was titrated to reduce Edi by 50%., Results: In order to achieve a 50% reduction in Edi, NPV required slightly more negative pressure (-8 to -12 cm H 2 O) than observed in PPV (+6 to +10 cm H 2 O). The efficiency of pressure transmission from the NeoVest into gastric pressure was 69.6% (range 61.3-77.4%). Swings in esophageal pressure were more negative during NPV than PPV, for all conditions, due to transmission of negative pressure. Transpulmonary pressure was lower during NPV. Transdiaphragmatic pressure swings were reduced similarly for PPV and NPV, suggesting equivalent unloading of the diaphragm. NPV did not affect hemodynamics., Conclusions: It is feasible to apply NPV sub-diaphragmatically in synchrony and in proportion to Edi in an animal model of respiratory distress., Impact: Negative pressure ventilation (NPV), for example, the "Iron Lung," may offer advantages over positive pressure ventilation. In the present work, we describe the "NeoVest," a system consisting of a sealed abdominal interface and a ventilator that applies NPV in synchrony and in proportion to the diaphragm electrical activity (Edi)., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

While transplantation is a viable treatment option for end-stage lung diseases, this option is highly constrained by the availability of organs and postoperative complications. A potential solution is the use of bioengineered lungs generated from repopulated acellular scaffolds. Effective recellularization, however, remains a challenge. In this proof-of-concept study, mice lung scaffolds were decellurized and recellurized using human bronchial epithelial cells (BEAS2B). We present a novel liquid ventilation protocol enabling control over tidal volume and high rates of ventilation. The use of a physiological tidal volume (300 μL) for mice and a higher ventilation rate (40 breaths per minute vs. 1 breath per minute) resulted in higher cell numbers and enhanced cell surface coverage in mouse lung scaffolds as determined via histological evaluation, genomic polymerase chain reaction (PCR) analysis, and immunohistochemistry. A biomimetic lung bioreactor system was designed to include the new ventilation protocol and allow for simultaneous vascular perfusion. We compared the lungs cultured in our dual system to lungs cultured with a bioreactor allowing vascular perfusion only and showed that our system significantly enhances cell numbers and surface coverage. In summary, our results demonstrate the importance of the physical environment and forces for lung recellularization. Impact statement New bioreactor systems are required to further enhance the regeneration process of bioengineered lungs. This proof-of-concept study describes a novel ventilation protocol that allows for control over ventilation parameters such as rate and tidal volume. Our data show that a higher rate of ventilation is correlated with higher cell numbers and increased surface coverage. We designed a new biomimetic bioreactor system that allows for ventilation and simultaneous perfusion. Compared to a traditional perfusion only system, recellularization was enhanced in lungs recellularized with our new biomimetic bioreactor.

Patient-ventilator asynchrony is very common in newborns. Achieving synchrony is quite challenging because of small tidal volumes, high respiratory rates, and the presence of leaks. Leaks also cause unreliable monitoring of respiratory metrics. In addition, ventilator adjustment must take into account that infants have strong vagal reflexes and demonstrate central apnea and periodic breathing, with a high variability in breathing pattern. Neurally adjusted ventilatory assist (NAVA) is a mode of ventilation whereby the timing and amount of ventilatory assist is controlled by the patient's own neural respiratory drive. As NAVA uses the diaphragm electrical activity (Edi) as the controller signal, it is possible to deliver synchronized assist, both invasively and noninvasively (NIV-NAVA), to follow the variability in breathing pattern, and to monitor patient respiratory drive, independent of leaks. This article provides an updated review of the physiology and the scientific literature pertaining to the use of NAVA in children (neonatal and pediatric age groups). Both the invasive NAVA and NIV-NAVA publications since 2016 are summarized, as well as the use of Edi monitoring. Overall, the use of NAVA and Edi monitoring is feasible and safe. Compared with conventional ventilation, NAVA improves patient-ventilator interaction, provides lower peak inspiratory pressure, and lowers oxygen requirements. Evidence from several studies suggests improved comfort, less sedation requirements, less apnea, and some trends toward reduced length of stay and more successful extubation., Competing Interests: Disclosure Drs J. Beck and C. Sinderby have made inventions related to neural control of mechanical ventilation that are patented. The patents are assigned to the academic institution(s) where inventions were made. The license for these patents belongs to Maquet Critical Care. Future commercial uses of this technology may provide financial benefit to Dr J. Beck and Dr C. Sinderby through royalties. Dr J. Beck and Dr C. Sinderby each own 50% of Neurovent Research Inc (NVR). NVR is a research and development company that builds the equipment and catheters for research studies. NVR has a consulting agreement with Maquet Critical Care., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Prolonged ventilatory support is associated with poor clinical outcomes. Partial support modes, especially pressure support ventilation, are frequently used in clinical practice but are associated with patient-ventilation asynchrony and deliver fixed levels of assist. Neurally adjusted ventilatory assist (NAVA), a mode of partial ventilatory assist that reduces patient-ventilator asynchrony, may be an alternative for weaning. However, the effects of NAVA on weaning outcomes in clinical practice are unclear., Methods: We searched PubMed, Embase, Medline, and Cochrane Library from 2007 to December 2020. Randomized controlled trials and crossover trials that compared NAVA and other modes were identified in this study. The primary outcome was weaning success which was defined as the absence of ventilatory support for more than 48 h. Summary estimates of effect using odds ratio (OR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with accompanying 95% confidence interval (CI) were expressed., Results: Seven studies (n = 693 patients) were included. Regarding the primary outcome, patients weaned with NAVA had a higher success rate compared with other partial support modes (OR = 1.93; 95% CI 1.12 to 3.32; P = 0.02). For the secondary outcomes, NAVA may reduce duration of mechanical ventilation (MD = - 2.63; 95% CI - 4.22 to - 1.03; P = 0.001) and hospital mortality (OR = 0.58; 95% CI 0.40 to 0.84; P = 0.004) and prolongs ventilator-free days (MD = 3.48; 95% CI 0.97 to 6.00; P = 0.007) when compared with other modes., Conclusions: Our study suggests that the NAVA mode may improve the rate of weaning success compared with other partial support modes for difficult to wean patients.

Background: In patients intubated for mechanical ventilation, prolonged diaphragm inactivity could lead to weakness and poor outcome. Time to resume a minimal diaphragm activity may be related to sedation practice and patient severity., Methods: Prospective observational study in critically ill patients. Diaphragm electrical activity (EAdi) was continuously recorded after intubation looking for resumption of a minimal level of diaphragm activity (beginning of the first 24 h period with median EAdi > 7 µV, a threshold based on literature and correlations with diaphragm thickening fraction). Recordings were collected until full spontaneous breathing, extubation, death or 120 h. A 1 h waveform recording was collected daily to identify reverse triggering., Results: Seventy-five patients were enrolled and 69 analyzed (mean age ± standard deviation 63 ± 16 years). Reasons for ventilation were respiratory (55%), hemodynamic (19%) and neurologic (20%). Eight catheter disconnections occurred. The median time for resumption of EAdi was 22 h (interquartile range 0-50 h); 35/69 (51%) of patients resumed activity within 24 h while 4 had no recovery after 5 days. Late recovery was associated with use of sedative agents, cumulative doses of propofol and fentanyl, controlled ventilation and age (older patients receiving less sedation). Severity of illness, oxygenation, renal and hepatic function, reason for intubation were not associated with EAdi resumption. At least 20% of patients initiated EAdi with reverse triggering., Conclusion: Low levels of diaphragm electrical activity are common in the early course of mechanical ventilation: 50% of patients do not recover diaphragmatic activity within one day. Sedatives are the main factors accounting for this delay independently from lung or general severity. Trial Registration ClinicalTrials.gov (NCT02434016). Registered on April 27, 2015. First patients enrolled June 2015.

Background: Veno-venous extracorporeal CO 2 removal (vv-ECCO 2 R) and non-invasive neurally adjusted ventilator assist (NIV-NAVA) are two promising techniques which may prevent complications related to prolonged invasive mechanical ventilation in patients with acute exacerbation of COPD., Methods: A physiological study of the electrical activity of the diaphragm (Edi) response was conducted with varying degrees of extracorporeal CO 2 removal to control the respiratory drive in patients with severe acute exacerbation of COPD breathing on NIV-NAVA., Results: Twenty COPD patients (SAPS II 37 ± 5.6, age 57 ± 9 years) treated with vv-ECCO 2 R and supported by NIV-NAVA were studied during stepwise weaning of vv-ECCO 2 R. Based on dyspnea, tolerance, and blood gases, weaning from vv-ECCO 2 R was successful in 12 and failed in eight patients. Respiratory drive (measured via the Edi) increased to 19 ± 10 μV vs. 56 ± 20 μV in the successful and unsuccessful weaning groups, respectively, resulting in all patients keeping their CO 2 and pH values stable. Edi was the best predictor for vv-ECCO 2 R weaning failure (ROC analysis AUC 0.95), whereas respiratory rate, rapid shallow breathing index, and tidal volume had lower predictive values. Eventually, 19 patients were discharged home, while one patient died. Mortality at 90 days and 180 days was 15 and 25%, respectively., Conclusions: This study demonstrates for the first time the usefulness of the Edi signal to monitor and guide patients with severe acute exacerbation of COPD on vv-ECCO 2 R and NIV-NAVA. The Edi during vv-ECCO 2 R weaning was found to be the best predictor of tolerance to removing vv-ECCO 2 R.

Introduction: Application of mechanical ventilation in spontaneously breathing children remains a challenge for several reasons: mainly, small tidal volumes and high respiratory rates, especially in the presence of leaks, interfere with patient-ventilator synchrony. Leaks also cause unreliable monitoring of respiratory drive and respiratory rate. Furthermore, ventilator adjustment must take into account that infants have strong vagal reflexes, demonstrate central apnea and periodic breathing, with a high variability in breathing pattern. Neurally-adjusted ventilatory assist (NAVA) is a mode of ventilation whereby the timing and amount of ventilatory assist is controlled by the patient's neural respiratory drive. Since NAVA uses the diaphragm electrical activity (Edi) as the controller signal, it is possible to deliver synchronized assist, both invasively and non-invasively (NIV-NAVA), to follow the variability in breathing pattern, and to monitor patient respiratory drive, independent of leaks., Evidence Acquisition: This article provides a review of the scientific literature pertaining to the use of NAVA in children (neonatal and pediatric age groups). Both the invasive and non-invasive NAVA publications are summarized, as well as the use of Edi monitoring., Evidence Synthesis: Overall, the use of NAVA and Edi monitoring is feasible and safe. Compared to conventional ventilation, NAVA improves patient-ventilator interaction, and provides lower peak inspiratory pressure., Conclusions: Evidence from a few trials suggests improved comfort, less sedation, and reduced length of stay.