Fourteen infants were studied with a mean (SD) gestational age (GA) at birth of 30,6 (3,5) weeks (range 25 4/7 to 35 2/7 weeks), birth weight (BW) of 1454 (667) g (range 580 to 2570 g) and age at the time of the study of 1,3 (0,6) days (range 1 to 3 days). Baseline characteristics and ventilator settings of enrolled infants are detailed in Table 1.
Table 1
Infant characteristics and baseline settings
Characteristics | N = 12 |
Gestational age at birth, mean weeks (SD, range) − 24–27 6/7 weeks, n − 28–31 6/7 weeks, n − 32–36 6/7 weeks, n | 30,6 (3,5, 25 4/7–35 2/7) 3 4 5 |
Births weight, mean grams (SD, range) | 1454 (667, 580–2570) |
Age at the time of the study, mean days (SD, range) | 1,3 (0,6, 1–3) |
Surfactant therapy, n (%) | 8 (75) |
Caffeine, n (%) | 8 (75) |
Baseline NAVA settings, mean (SD) - NAVA level (cmH2O/µV) - PEEP (cmH2O) - FiO2 (%) - Apnea time (s) | 1,3 (0,3) 6,2 (0,4) 24 (5) 3,5 (0,9) |
Leakage during the study, mean % (SD) | 88,6 (7,4) |
Figure 1 shows changes in Edi and PIP according to the NAVA level for a representative patient for each age group. As the NAVA level is increased, PIP increases accordingly. At a specific NAVA level, further increases are no longer associated with increases in PIP, and Edi values start to decrease. The point at which this happens is called the breakpoint and could be identified in all patients. In some patients a second rise in PIP was noticed after the plateau phase had been reached. As seen in panel A of Fig. 1, a breakpoint can be identified at level 1,5, followed by a second rise in PIP at levels 3,5 and 4. This phenomenon was only observed in infants with a gestational age below 32 weeks. The rise in Edi that is normally expected to be found in the lower range of NAVA levels was absent or minimal in most of the patients, and there was no clear relation with gestational age.
Figure 2 shows the composite data of PIP and Edi for all patients, the breakpoint for the whole study group was at a mean (SD) NAVA level of 2,33 (0,58) cmH2O/µV (range 1,5 to 3,5 cmH2O/µV). The mean (SD) plateau PIP at the breakpoint was 15,2 (4,0) cmH2O. The combined data also show a secondary rise in PIP after the breakpoint with a mean (SD) maximum PIP of 16,5 (3,4) cmH2O. The NAVA level at the breakpoint was on average 1,03 cmH2O/µV (CI 0.62–1.45, p < 0,01) higher than the baseline NAVA level.
Mean (SD) RR was 65,0 (4,2) per minute, reflecting mild tachypnoea compatible with a population of preterm infants with RDS. A significant decrease of RR with increasing NAVA levels (p < 0,0001) was seen. On average, the RR decreased with 9,6 breaths per minute over the entire titration protocol. No relation between RR and the breakpoint was identified. Further inspection of the individual curves highlighted a strong variability in RR per patient during the study, as typical for preterm infants. There were no significant changes in HR, SpO2 and FiO2 during the study. HR was always within normal range (100 to 180 bpm) and on average (SD) 139 (8,3) beats per minute, no bradycardic events occurred. SpO2 was on average (SD) 95,6 (3,3) %. In two patients, mild desaturation occurred with a minimal oxygen saturation of 86% for less than 30 seconds. For most patients FiO2 was stable during the protocol with an average (SD) FiO2 of 24,1 (5,8) %. In one patient (GA 35 weeks, BW 2240g), with severe RDS, a temporary rise in FiO2 from 38–55% was needed to keep the oxygen saturation within the target range, this was seen at levels 2 and 2,5 cmH2O /µV. No severe complications occurred.