Clinical Application And Mechanism Research Of Neurally Adjusted Ventilatory Assist In Neonatal Respiratory Failure With Mechanical Ventilation

Part one:Application of neurally adjusted ventilatory assist in preterm infants with respiratory distress syndromeObjective:To observe the effects of neurally adjusted ventilatory assist (NAVA) on the gas exchange, ventilatory parameters and patient-ventilator synchrony in preterm infants with respiratory distress syndrome (RDS) during mechanical ventilation.Methods:Ten preterm infants with RDS received mechanical ventilation in NAVA mode for 60 minutes and in synchronized intermittent mandatory ventilation (SIMV) mode for 60 minutes, and the two modes were given in a random order. The parameters of gas exchange (pH, PaCO2, PaO2, FiO2, PaO2/FiO2), respiratory mechanics (spontaneous respiratory rate, mean airway pressure, peak inspiratory pressure (PIP), electrical activity of the diaphragm (EAdi), minute volume of inspiratory (MVi), tidal volume of inspiratory (VTi), work of breathing), patient-ventilator synchrony (trigger delay (Td), cycle-off delay (Cd), neural inspiratory time (NTi), mechanical inspiratory time (MTi), △EAdi-Td, △EAdi-NTi) were compared between the two ventilation modes.Results:1. There were no significant differences in gas exchange between the two modes.2. There was a linear positive correlation between PIP and △EAdi-NTi (R2=0.757, p<0.05), MTi and NTi (R2=0.753,p<0.05) in NAVA.3. Respiratory mechanics:The spontaneous respiratory rate, PIP, peak and minimum of EAdi and work of breathing were significantly lower in NAVA than in SIMV (P<0.05). VTi/kg and VTi/EAdi-peak were significantly higher in NAVA than in SIMV (P<0.05).4. Patient-ventilator synchrony:(1) Neural inspiratory time and mechanical inspiratory time were significantly shorter in SIMV than in NAVA (P<0.05).(2) Inspiratory trigger delay and cycle-off delay were significantly longer in SIMV than in NAVA (P<0.05).(3) △EAdi-Td and △EAdi-NTi were greater in SIMV than in NAVA (P<0.05).(4) Td/NTi were higher in SIMV than in NAVA (P<0.05).Conclusions:NAVA can be applied in preterm infants with RDS effectively. Compared with SIMV, NAVA appears to improve patient-ventilator synchrony, decreases PIP, and reduces diaphragmatic muscle load and work of breathing in preterm infants with RDS during mechanical ventilation.Part two:Effects of NAVA on ventilatory parameters and patient-ventilator synchrony in newborn rabbits with mechanical ventilationObjective:To observe the effects of neurally adjusted ventilatory assist (NAVA) on the ventilatory parameters and patient-ventilator synchrony in newborn rabbits with mechanical ventilation.Methods:Twenty-four newborn rabbits were randomly divided into 4 groups:normal control group (n=6), NAVA group (n=6), PSV (pressure support ventilation) group (n=6), PCV (pressure control ventilation) group (n=6). Three mechanical ventilation groups underwent an incremental pressure in four steps:NAVA level was gradually increased 1.0cmH2O/μV every 10min from 1.0cmH2O/μV until 4.0cmH2O/μV; PSV and PCV level were gradually increased 5cmH2O every l0min from 5cmH2O until 20cmH2O; then three groups were adjusted initial setting as similar PIP and ventilated for 6 hours. The variations of ventilatory parameters andpatient-ventilator synchrony were observed between different pressures and ventilation modes.Results:1. The effects on ventilatory parameters between different pressures:(1) EAdi-peak, △EAdi-NTi and neutrally respiratory rate decreased gradually with progressive rising level in three ventilation groups (p<0.05).(2) In NAVA group, there was a linear positive correlation between PIP and △EAdi-NTi×NAVA level (R2=0.921,p<0.05). PIP and VTi did not increase proportionally with pressure level. There were no significant differences in △EAdi-Td between different NAVA levels.(3) In PSV group and PCV group, PIP and VTi increased proportionally with ascending pressure level (p<0.05). △EAdi-Td of PSV 5cmH2O was greater than other three PSV level (p<0.05).2. The effects on patient-ventilator synchrony between different pressures:(1) There were no significant differences in trigger delay, cycle-off delay, neural and mechanical inspiratory time between different NAVA levels.(2) In PSV group, neural inspiratory time was gradually prolonged and cycle-off delay was gradually shortened with increasing PSV level (p<0.05), even appeared too early cycle-off. There were no significant differences in trigger delay and mechanical inspiratory time between different PSV levels.(3) In PCV group, neural inspiratory time was gradually prolonged wth increasing PCV level (p<0.05). There were no significant differences in mechanical inspiratory time between different PCV levels. The uneffective triggers (trigger without EAdi and EAdi without trigger) occured in addition to cycle-off delay and early. Asynchrony Index fluctuated from 36.67% to 54.17% between different PCV levels but there were no statistical differences (p>0.05).3. The ventilatory parameters and patient-ventilator synchrony in three modes:(1) Ventilatory parameters:PIP, EAdi-peak, △EAdi-NTi and neural inspiratory time in NAVA group were significantly lower than PSV and PCV group after 6 hours ventilated (p<0.05). △EAdi-Td and △EAdi-NTi in PCV group were significantly greater than other two modes (p<0.05). Neural respiratory rate in PSV group was higher than other two modes (p<0.05). There were no significant differences in VTi and EAdi-min between three modes.(2) Patient-ventilator synchrony:Compared with PSV and PCV, the trigger delay, Td/NTi and △EAdi-Td/AEAdi-NTi deceased, and cycle-off delay, neural and mechanical inspiratory time were longer in NAVA (p<0.05).4. Coefficient of variationin (CV) between three modes:The CV of PIP, VTi, △EAdi-NTi, and mechanical inspiratory time in NAVA were higher than PSV and PCV (p<0.05). In the contrary, CV of trigger delay, cycle-off delay, △EAdi-Td, Td/NTi and △EAdi-Td/△EAdi-NTi in NAVA were lower than PSV and PCV (p<0.05).Conclusions:1. In three modes, EAdi and neural respiratory rate had a trend of gradual reduction with increasing pressure support level. High PSV and PCV level were more likely to over-supported and inhibit respiratory. EAdi and neural respiratory rate could be contributed to the ventilator pressure setting and adjustment.2. The synchrony was similar in different NAVA levels, but the variations of synchrony was greater and asynchrony was significant in different PSV and PCV levels.3. The respiratory loading decreased and synchrony was improved in NAVA compared with PSV and PCV.4. The ventilatory parameters in NAVA were more correspond with physiological changes in respiratory and the variations of synchrony were more stable.Part three:Effects of NAVA on ultrastructure and cell apoptosis of diaphragm in newborn rabbitsObjective:To evaluate the effects of neurally adjusted ventilatory assist (NAVA) on the ultrastructure and cell apoptosis of diaphragm in newborn rabbits.Methods:Forty-two newborn rabbits were randomly divided into seven groups (n=6 in each group):1. normal control without ventilation,2. NAVA modes for 3 hours (NAVA 3H), 3. NAVA modes for 6 hours (NAVA 6H),4. PSV modes for 3 hours (PSV 3H),5. PSV modes for 6 hours (PSV 6H),6. PCV modes for 3 hours (PCV 3H),7. PCV modes for 6 hours (PCV 6H). The rabbtits in the ventilation groups were intubated with tracheostomy after intraperitoneal anesthesia. NAVA ventilator setting:EAdi trigger 0.5μV, cycle-off 70% of EAdi-peak, FiO2 21%, PEEP 2cmH2O, NAVA level was adjusted until PIP was matched to PSV and PCV (2.5-3.0 cmH20/μV); PSV ventilator setting:flow trigger 0.3L/min, Esens 20%, FiO2 21%, PEEP 2cmH2O, PS above PEEP 15cmH2O; PCV ventilator setting:Ti 0.33 second, FiO2 21%, PEEP 2cmH2O, PC above PEEP 15cmH2O, mechanical ventilation rate 40 bpm. The diaphragm ultrastructure was assessed by transmission electron microscopy and the diaphragm cell apoptosis was evaluated by transferase-mediated d-UTP nick-end labeling (TUNEL) and the expression of Caspase-3 mRNA was detected through RT-PCR analysis.Results:1. Diaphragmtic ultrastructure injury:After 3 hours ventilated, the three ventilation groups had slight injury. The muscle fibrils were neatly arranged, sarcomere integrity was maintained, some of the Z lines were fuzzy, mitochondria appeared to be swelling. A number of lipid vacuoles were observed in PSV 3H group. There was obviously mitochondria swelling along with crist deformation in PCV 3H group. After 6 hours ventilated, myofilament was loose arrangement and mitochondria swelling was aggravated in NAVA 6H group and PSV 6H group. A large amount of lipid vacuoles were observed in PSV 6H group. The PCV 6H group had the most serious structure injury. Some parts of myofibrils were irregular, dissolved and cracked. Some parts of Z lines had a blurred appearance along with structural disorder. Mitochondria swelling was remarkable along with membrane disappeared and medullary degeneration.2. Diaphragmtic cell apoptosis:The apoptotic cell proportion detected by TUNEL techniques was significantly increased in the PCV 3H group than in the NAVA 3H group and PSV 3H group (p<0.05). There were significantly higher percents of apoptotic cell in ventilated 6H groups compared with ventilated 3H groups relatively (p<0.05). The apoptosis indexes of NAVA 6H group and PSV 6H group were significantly lower than PCV 6H group (p<0.05).3. Expression of Caspase-3 mRNA:There were no significant differences of expression of Caspase-3 mRNA between ventilated 3H groups, but the expression level of PCV 3H group was significantly higher than normal control group (p<0.05). There were significantly increased expression in ventilated 6H groups compared with ventilated 3H groups relatively and normal control group (p<0.05). The expression level of PCV 6H group was significantly increased compared with NAVA 6H group and PSV 6H group (p<0.05).Conclusions:1. Compared with PCV, NAVA and PSV may mitigate structure injury of diaphragmatic fiber during mechanical ventilation.2. Diaphragmtic cell apoptosis appeared in the early stage of mechanical ventilation. The proportion of apoptotic cell was increased with prolonged ventilation. PCV can aggravate the apoptosis index compared with NAVA and PSV.3. The expression of Caspase-3 mRNA of diaphragm was increased with prolonged ventilation. NAVA and PSV can reduce the expression level of Caspase-3 mRNA of diaphragm.4. The partial support ventilation is likely to have more advantage of preventing ventilator-induced diaphragmatic dysfunction over the control mechanical ventilation.