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Background Prolonged controlled mechanical ventilation depresses diaphragmatic efficiency. Assisted modes of ventilation should improve it. We assessed the impact of pressure support ventilation versus neurally adjusted ventilator assist on diaphragmatic efficiency. Method Patients previously ventilated with controlled mechanical ventilation for 72 hours or more were randomized to be ventilated for 48 hours with pressure support ventilation (n =12) or neurally adjusted ventilatory assist (n = 13). Neuro-ventilatory efficiency (tidal volume/diaphragmatic electrical activity) and neuro-mechanical efficiency (pressure generated against the occluded airways/diaphragmatic electrical activity) were measured during three spontaneous breathing trials (0, 24 and 48 hours). Breathing pattern, diaphragmatic electrical activity and pressure time product of the diaphragm were assessed every 4 hours. Results In patients randomized to neurally adjusted ventilator assist, neuro-ventilatory efficiency increased from 27 ± 19 ml/μV at baseline to 62 ± 30 ml/μV at 48 hours (p <0.0001) and neuro-mechanical efficiency increased from 1 ± 0.6 to 2.6 ± 1.1 cmH 2 O/μV (p = 0.033). In patients randomized to pressure support ventilation, these did not change. Electrical activity of the diaphragm, neural inspiratory time, pressure time product of the diaphragm and variability of the breathing pattern were significantly higher in patients ventilated with neurally adjusted ventilatory assist. The asynchrony index was 9.48 [6.38– 21.73] in patients ventilated with pressure support ventilation and 5.39 [3.78– 8.36] in patients ventilated with neurally adjusted ventilatory assist (p = 0.04). Conclusion After prolonged controlled mechanical ventilation, neurally adjusted ventilator assist improves diaphragm efficiency whereas pressure support ventilation does not. Trial registration ClinicalTrials.gov study registration: NCT0247317 , 06/11/2015.

Background The clinical effectiveness of neurally adjusted ventilatory assist (NAVA) has yet to be demonstrated, and preliminary studies are required. The study aim was to assess the feasibility of a randomized controlled trial (RCT) of NAVA versus pressure support ventilation (PSV) in critically ill adults at risk of prolonged mechanical ventilation (MV). Methods An open-label, parallel, feasibility RCT ( n  = 78) in four ICUs of one university-affiliated hospital. The primary outcome was mode adherence (percentage of time adherent to assigned mode), and protocol compliance (binary—≥ 65% mode adherence). Secondary exploratory outcomes included ventilator-free days (VFDs), sedation, and mortality. Results In the 72 participants who commenced weaning, median (95% CI) mode adherence was 83.1% (64.0–97.1%) and 100% (100–100%), and protocol compliance was 66.7% (50.3–80.0%) and 100% (89.0–100.0%) in the NAVA and PSV groups respectively. Secondary outcomes indicated more VFDs to D28 (median difference 3.0 days, 95% CI 0.0–11.0; p  = 0.04) and fewer in-hospital deaths (relative risk 0.5, 95% CI 0.2–0.9; p  = 0.032) for NAVA. Although overall sedation was similar, Richmond Agitation and Sedation Scale (RASS) scores were closer to zero in NAVA compared to PSV ( p  = 0.020). No significant differences were observed in duration of MV, ICU or hospital stay, or ICU, D28, and D90 mortality. Conclusions This feasibility trial demonstrated good adherence to assigned ventilation mode and the ability to meet a priori protocol compliance criteria. Exploratory outcomes suggest some clinical benefit for NAVA compared to PSV. Clinical effectiveness trials of NAVA are potentially feasible and warranted. Trial registration ClinicalTrials.gov , NCT01826890 . Registered 9 April 2013.

Purpose To determine if neurally adjusted ventilatory assist (NAVA) improves asynchrony, ventilatory drive, breath-to-breath variability and COMFORT score when compared to pressure support (PS). Methods This is a non-randomized short-term cross-over trial in which 12 pediatric patients with asynchrony (auto-triggering, double triggering or non-triggered breaths) were enrolled. Four sequential 10-min periods of data were recorded after 20 min of ventilatory stabilization (wash-out) at each of the following settings: baseline PS with the ventilator settings determined by the attending physician (1-PS b ); PS after optimization (2-PS opt ); NAVA level set so that maximum inspiratory pressure ( P max ) equaled P max in PS (3-NAVA); same settings as in 2-PS opt (4-PS opt ). Results The median asynchrony index was significantly lower during NAVA (2.0 %) than during 2-PS opt (8.5 %, p  = 0.017) and 4-PS opt (7.5 %, p  = 0.008). In NAVA mode, the NAVA trigger accounted on average for 66 % of triggered breaths. The median trigger delay with respect to neural inspiratory time was significantly lower during NAVA (8.6 %) than during 2-PS opt (25.2 %, p  = 0.003) and 4-PS opt (28.2 %, p  = 0.0005). The median electrical activity of the diaphragm (EAdi) change during trigger delay normalized to maximum inspiratory EAdi difference was significantly lower during NAVA (5.3 %) than during 2-PS opt (21.7 %, p  = 0.0005) and 4-PS opt (24.6 %, p  = 0.001). The coefficient of variation of tidal volume was significantly higher during NAVA (44.2 %) than during 2-PS opt (19.8 %, p  = 0.0002) and 4-PS opt (23.0 %, p  = 0.0005). The median COMFORT score during NAVA (15.0) was lower than that during 2-PS opt (18.0, p  = 0.0125) and 4-PS opt (17.5, p  = 0.039). No significant changes for any variable were observed between 1-PS b and 2-PS opt . Conclusions Neurally adjusted ventilatory assist as compared to optimized PS results in improved synchrony, reduced ventilatory drive, increased breath-to-breath mechanical variability and improved patient comfort.

Background Poor patient-ventilator synchronization is often observed during pressure support ventilation (PSV) and has been associated with prolonged duration of mechanical ventilation and poor outcome. Diaphragmatic electrical activity (Eadi) recorded using specialized nasogastric tubes is a surrogate of respiratory brain stem output. This study aimed at testing whether adapting ventilator settings during PSV using a protocolized Eadi-based optimization strategy, or Eadi-triggered and -cycled assisted pressure ventilation (or PSV N ) could (1) improve patient-ventilator interaction and (2) reduce or normalize patient respiratory effort as estimated by the work of breathing (WOB) and the pressure time product (PTP). Methods This was a prospective cross-over study. Patients with a known chronic pulmonary obstructive or restrictive disease, asynchronies or suspected intrinsic positive end-expiratory pressure (PEEP) who were ventilated using PSV were enrolled in the study. Four different ventilator settings were sequentially applied for 15 minutes (step 1: baseline PSV as set by the clinician, step 2: Eadi-optimized PSV to adjust PS level, inspiratory trigger, and cycling settings, step 3: step 2 + PEEP adjustment, step 4: PSV N ). The same settings as step 3 were applied again after step 4 to rule out a potential effect of time. Breathing pattern, trigger delay (T d ), inspiratory time in excess (T iex ), pressure-time product (PTP), and work of breathing (WOB) were measured at the end of each step. Results Eleven patients were enrolled in the study. Eadi-optimized PSV reduced T d without altering T iex in comparison with baseline PSV. PSV N reduced T d and T iex in comparison with baseline and Eadi-optimized PSV. Respiratory pattern did not change during the four steps. The improvement in patient-ventilator interaction did not lead to changes in WOB or PTP. Conclusions Eadi-optimized PSV allows improving patient ventilator interaction but does not alter patient effort in patients with mild asynchrony. Trial registration Clinicaltrials.gov identifier: NCT 02067403 . Registered 7 February 2014.

Background If the proportional assist ventilation (PAV) level is known, muscular effort can be estimated from the difference between peak airway pressure and positive end-expiratory pressure (PEEP) (ΔP) during PAV. We conjectured that deducing muscle pressure from ΔP may be an interesting method to set PAV, and tested this hypothesis using the oesophageal pressure time product calculation. Methods Eleven mechanically ventilated patients with oesophageal pressure monitoring under PAV were enrolled. Patients were randomly assigned to seven assist levels (20–80%, PAV20 means 20% PAV gain) for 15 min. Maximal muscular pressure calculated from oesophageal pressure (P mus, oes ) and from ΔP (P mus, aw ) and inspiratory pressure time product derived from oesophageal pressure (PTP oes ) and from ΔP (PTP aw ) were determined from the last minute of each level. P mus, oes and PTP oes with consideration of PEEPi were expressed as P mus, oes, PEEPi and PTP oes, PEEPi , respectively. Pressure time product was expressed as per minute (PTP oes , PTP oes, PEEPi , PTP aw ) and per breath (PTP oes, br , PTP oes, PEEPi, br , PTP aw, br ). Results PAV significantly reduced the breathing effort of patients with increasing PAV gain (PTP oes 214.3 ± 80.0 at PAV20 vs. 83.7 ± 49.3 cmH 2 O•s/min at PAV80, PTP oes, PEEPi 277.3 ± 96.4 at PAV20 vs. 121.4 ± 71.6 cmH 2 O•s/min at PAV80, p  < 0.0001). P mus, aw overestimates P mus, oes for low-gain PAV and underestimates P mus, oes for moderate-gain to high-gain PAV. An optimal P mus, aw could be achieved in 91% of cases with PAV60. When the PAV gain was adjusted to P mus, aw of 5–10 cmH 2 O, there was a 93% probability of PTP oes <224 cmH 2 O•s/min and 88% probability of PTP oes, PEEPi  < 255 cmH 2 O•s/min. Conclusion Deducing maximal muscular pressure from ΔP during PAV has limited accuracy. The extrapolated pressure time product from ΔP is usually less than the pressure time product calculated from oesophageal pressure tracing. However, when the PAV gain was adjusted to P mus, aw of 5–10 cmH 2 O, there was a 90% probability of PTP oes and PTP oes, PEEPi within acceptable ranges. This information should be considered when applying ΔP to set PAV under various gains.

Purpose To compare patient–ventilator interaction during PSV and PAV+ in patients that are difficult to wean. Methods This was a physiologic study involving 11 patients. During three consecutive trials (PSV first trial—PSV1, followed by PAV+, followed by a second PSV trial—PSV2, with the same settings as PSV1) we evaluated mechanical and patient respiratory pattern; inspiratory effort from excursion Pdi (swing Pdi ), and pressure–time products of the transdiaphragmatic (PTPdi) pressures. Inspiratory (delay trinsp ) and expiratory (delay trexp ) trigger delays, time of synchrony (time syn ), and asynchrony index (AI) were assessed. Results Compared to PAV+, during PSV trials, the mechanical inspiratory time (Ti flow ) was significantly longer than patient inspiratory time (Ti pat ) ( p  < 0.05); Ti pat showed a prolongation between PSV1 and PAV+, significant comparing PAV+ and PSV2 ( p  < 0.05). PAV+ significantly reduced delay trexp ( p  < 0.001). The portion of tidal volume (VT) delivered in phase with Ti pat (VT pat /VT mecc ) was significantly higher during PAV+ ( p  < 0.01). The time of synchrony was significantly longer during PAV+ than during PSV ( p  < 0.001). During PSV 5 patients out of 11 showed an AI greater than 10%, whereas the AI was nil during PAV+. Conclusion PAV+ improves patient–ventilator interaction, significantly reducing the incidence of end-expiratory asynchrony and increasing the time of synchrony.

Purpose Diaphragmatic electrical activity (EA di ), reflecting respiratory drive, and its feedback control might be impaired in critical illness-associated polyneuromyopathy (CIPM). We aimed to evaluate whether titration and prolonged application of neurally adjusted ventilatory assist (NAVA), which delivers pressure ( P aw ) in proportion to EA di , is feasible in CIPM patients. Methods Peripheral and phrenic nerve electrophysiology studies were performed in 15 patients with clinically suspected CIPM and in 14 healthy volunteers. In patients, an adequate NAVA level (NAVAal) was titrated daily and was implemented for a maximum of 72 h. Changes in tidal volume ( V t ) generation per unit of EA di ( V t /EA di ) were assessed daily during standardized tests of neuro-ventilatory efficiency (NVET). Results In patients (median [range], 66 [44–80] years), peripheral electrophysiology studies confirmed CIPM. Phrenic nerve latency (PNL) was prolonged and diaphragm compound muscle action potential (CMAP) was reduced compared with healthy volunteers ( p  < 0.05 for both). NAVAal could be titrated in all but two patients. During implementation of NAVAal for 61 (37–64) h, the EA di amplitude was 9.0 (4.4–15.2) μV, and the V t was 6.5 (3.7–14.3) ml/kg predicted body weight. V t , respiratory rate, EA di , PaCO 2 , and hemodynamic parameters remained unchanged, while PaO 2 /FiO 2 increased from 238 (121–337) to 282 (150–440) mmHg ( p  = 0.007) during NAVAal. V t /EA di changed by −10 (−46; +31)% during the first NVET and by −0.1 (−26; +77)% during the last NVET ( p  = 0.048). Conclusion In most patients with CIPM, EA di and its feedback control are sufficiently preserved to titrate and implement NAVA for up to 3 days. Whether monitoring neuro-ventilatory efficiency helps inform the weaning process warrants further evaluation.

Seven of the children included (median age 35 [27–63] days) had a respiratory recording during the transition from nasal continuous positive airway pressure (nCPAP; set at 7cmH2O [4]) to NAVA. Table 1 Comparison of physiological parameters between nasal continuous positive airway pressure and neutrally adjusted ventilatory assist nCPAP NAVA p* Ti/Ttot (%) 0.47 [0.45–0.49] 0.40 [0.37–0.45] 0.02 Respiratory rate (/min) 71 [64–84] 65 [57–80] 0.31 Mean airway pressure (cmH2O) 7.0 [6.9–7.1] 10.6 [9.4–11.9] 0.02 ΔEdi (μV) 19 [17–25] 16 [10–19] 0.03 Swing Peso (cmH2O) 14 [12–18] 8 [8–13] 0.01 Swing Pdi (cmH2O) 14 [13–15] 10 [9–10] 0.02 PTPeso/breath (cmH2O s) 4.7 [3.4–6.1] 2.1 [1.9–3.7] 0.02 PTPdi/breath (cmH2O s) 4.2 [3.9–4.4] 2.6 [2.5–2.8] 0.02 PTPeso/min (cmH2O s/min) 365 [237–429] 162 [139–226] 0.02 PTPdi/min (cmH2O s/min) 298 [256–354] 157 [151–199] 0.02 Data are expressed as median [interquartile range] nCPAP nasal continuous positive airway pressure, NAVA neutrally adjusted ventilatory assist, PEEP positive end expiratory pressure, Ti inspiratory time, Ttot total time, Peso esophageal pressure, Pga gastric pressure, Edi electrical activity of the diaphragm, PTP pressure time product *Wilcoxon two-sample paired sign test Fig. 1 Fig. 1 Fig. 1 Decrease of esophageal and trans-diaphragmatic pressure swing and Edi amplitude after switching to neurally adjusted ventilatory assist. The red arrow indicates the switch from nCPAP to NAVA. nCPAP, nasal continuous positive airway pressure; NAVA, neurally adjusted ventilatory assist; PEEP, positive end expiratory pressure; Paw, airway pressure; Peso, esophageal pressure; Pga, gastric pressure; EAdi, electrical activity of the diaphragm In this physiological study, we report an improvement of respiratory unloading by adding a second level of pressure with NAVA in infants with severe bronchiolitis.

Background Double cycling with breath-stacking (DC/BS) during controlled mechanical ventilation is considered potentially injurious, reflecting a high respiratory drive. During partial ventilatory support, its occurrence might be attributable to physiological variability of breathing patterns, reflecting the response of the mode without carrying specific risks. Methods This secondary analysis of a crossover study evaluated DC/BS events in hypoxemic patients resuming spontaneous breathing in cross-over under neurally adjusted ventilatory assist (NAVA), proportional assist ventilation (PAV +), and pressure support ventilation (PSV). DC/BS was defined as two inspiratory cycles with incomplete exhalation. Measurements included electrical impedance signal, airway pressure, esophageal and gastric pressures, and flow. Breathing variability, dynamic compliance (C L dyn), and end-expiratory lung impedance (EELI) were analyzed. Results Twenty patients under assisted breathing, with a median of 9 [5–14] days on mechanical ventilation, were included. DC/BS was attributed to either a single (42%) or two apparent consecutive inspiratory efforts (58%). The median [IQR] incidence of DC/BS was low: 0.6 [0.1–2.6] % in NAVA, 0.0 [0.0–0.4] % in PAV + , and 0.1 [0.0–0.4] % in PSV ( p  = 0.06). DC/BS events were associated with patient’s coefficient of variability for tidal volume ( p  = 0.014) and respiratory rate ( p  = 0.011). DC/BS breaths exhibited higher tidal volume, muscular pressure and regional stretch compared to regular breaths. Post-DC/BS cycles frequently exhibited improved EELI and C L dyn, with no evidence of expiratory muscle activation in 63% of cases. Conclusions DC/BS events during partial ventilatory support were infrequent and linked to breathing variability. Their frequency and physiological effects on lung compliance and EELI resemble spontaneous sighs and may not be considered a priori as harmful.