Feasibility of neurally adjusted positive end-expiratory pressure in rabbits with early experimental lung injury.

BACKGROUND: During conventional Neurally Adjusted Ventilatory Assist (NAVA), the electrical activity of the diaphragm (EAdi) is used for triggering and cycling-off inspiratory assist, with a fixed PEEP (so called "Triggered Neurally Adjusted Ventilatory Assist" or "tNAVA"). However, significant post-inspiratory activity of the diaphragm can occur, believed to play a role in maintaining end-expiratory lung volume. Adjusting pressure continuously, in proportion to both inspiratory and expiratory EAdi (Continuous NAVA, or cNAVA), would not only offer inspiratory assist for tidal breathing, but also may aid in delivering a "neurally adjusted PEEP", and more specific breath-by-breath unloading. METHODS: Nine adult New Zealand white rabbits were ventilated during independent conditions of: resistive loading (RES(1) or RES(2)), CO2 load (CO2) and acute lung injury (ALI), either via tracheotomy (INV) or non-invasively (NIV). There were a total of six conditions, applied in a non-randomized fashion: INV-RES(1), INV-CO2, NIV-CO2, NIV-RES(2), NIV-ALI, INV-ALI. For each condition, tNAVA was applied first (3 min), followed by 3 min of cNAVA. This comparison was repeated 3 times (repeated cross-over design). The NAVA level was always the same for both modes, but was newly titrated for each condition. PEEP was manually set to zero during tNAVA. During cNAVA, the assist during expiration was proportional to the EAdi. During all runs and conditions, ventilator-delivered pressure (Pvent), esophageal pressure (Pes), and diaphragm electrical activity (EAdi) were measured continuously. The tracings were analyzed breath-by-breath to obtain peak inspiratory and mean expiratory values. RESULTS: For the same peak Pvent, the distribution of inspiratory and expiratory pressure differed between tNAVA and cNAVA. For each condition, the mean expiratory Pvent was always higher (for all conditions 4.0 ± 1.1 vs. 1.1 ± 0.5 cmH2O, P < 0.01) in cNAVA than in tNAVA. Relative to tNAVA, mean inspiratory EAdi was reduced on average (for all conditions) by 19 % (range 14 %-25 %), p < 0.05. Mean expiratory EAdi was also lower during cNAVA (during INV-RES(1), INV-CO2, INV-ALI, NIV-CO2 and NIV-ALI respectively, P < 0.05). The inspiratory Pes was reduced during cNAVA all 6 conditions (p < 0.05). Unlike tNAVA, during cNAVA the expiratory pressure was comparable with that predicted mathematically (mean difference of 0.2 ± 0.8 cmH2O). CONCLUSION: Continuous NAVA was able to apply neurally adjusted PEEP, which led to a reduction in inspiratory effort compared to triggered NAVA.

Characterization of neural breathing pattern in spontaneously breathing preterm infants.

The aim was to characterize the neural breathing pattern in nonintubated preterm infants. The diaphragm electrical activity (EAdi) and heart rate were simultaneously measured repeatedly for 1 h over several days using a modified feeding tube equipped with miniaturized sensors. The EAdi waveform was quantified for phasic and tonic activity, neural timings, and prevalence of recurring patterns, including central apnea. Ten infants with mean age 7 d (range, 3-13 d) were studied. Their birth weight was 1512 g (1158-1800 g) and GA at birth 31 wk (28-36 wk). Neural inspiratory and expiratory times were 278 ms (195-450 ms) and 867 ms (668-1436 ms) and correlated with GA (p < 0.001). Tonic EAdi represented 29.5% of phasic EAdi (16-40%) and was related to GA (r = 0.61, p < 0.001). For the group, 68% of the time was regular phasic breathing (without tonic activity) and 29% of the time with elevated tonic activity. Central apneas >5 s occurred on average 10 times per hour (2-29). Heart rate reductions were correlated to central apnea duration. In conclusion, esophageal recordings of the EAdi waveform demonstrate that neural breathing pattern is variable, with regards to timing, amplitude, and pattern with a distinct amount of tonic diaphragm activity.

Physiological response to increasing levels of neurally adjusted ventilatory assist (NAVA).

This study evaluated the response to increasing levels of neurally adjusted ventilatory assist (NAVA), a mode converting electrical activity of the diaphragm (EAdi) into pressure, regulated by a proportionality constant called the NAVA level. Fourteen rabbits were studied during baseline, resistive loading and ramp increases of the NAVA level. EAdi, airway (Paw) and esophageal pressure (Pes), Pes pressure time product (PTPes), breathing pattern, and blood gases were measured. Resistive loading increased PTPes and EAdi. P(a)(CO)(2) increased with high load but not during low load. Increasing NAVA levels increased Paw until a breakpoint where the Paw increase was reduced despite increasing NAVA level. At this breakpoint, Pes, PTPes, EAdi, and P(a)(CO)(2) were similar to baseline. Further increase of the NAVA level reduced Pes, PTPes and EAdi without changes in ventilation. In conclusion, observing the trend in Paw during a ramp increase of the NAVA level allows determination of a level where the inspiratory effort matches unloaded conditions.

[Clinical efficacy and safety of itraconazole injection/oral solution sequential therapy for treatment of invasive fungal infection in intensive care unit].

OBJECTIVE: To investigate the therapeutic efficacy and safety of itraconazole injection/oral sequential therapy on invasive fungal infection (IFI) in ICU. METHODS: In this multicenter, post-marketing, open-label study, ICU patients who have met the inclusion IFI criteria will be enrolled in this study. Itraconazole intravenous injection is administered 200 mg twice a day in day 1 - 2, then 200 mg once a day at least for 5 days, and maintenance itraconazole oral solution as sequential therapy, itraconazole oral solution 200 mg twice a day sequential therapy lasts for 2 weeks. Clinical efficacy and adverse reaction were record. RESULTS: A total of 159 patients were enrolled and completed this trial. (1) At the end of first week, total clinical cure rate was 35.2%, and increased to 73.6% after the second week. Clinical cure rate were 72.9% and 72.2% in possible and probable IFI patients, and 78.9% in proven IFI patients at the end of second week. (2) At the end of first week, total fungal clearance was 40.9%, and increased to 75.9% and 92.9% at the end of second and fourth week. Fungal clearance were 90.0% and 64.6% in possible and probable IFI patients, and 84.2% in proven IFI patients at the end of second week respectively. (3) Combined clinical cure rate and fungal clearance, the total clinic efficacy was 44.1% at the end of first week, and increased to 92.9% and 100.0% at the end of second and fourth week. (4) No severe adverse reaction was found. CONCLUSIONS: Itraconazole injection/oral sequential therapy is an effective and safe antibiotic for the treatment of IFI in ICU.