The Effect of NIV NAVA 0 on Ventilation in Premature Neonates

doi:10.21203/rs.3.rs-1004905/v1

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The Effect of NIV NAVA 0 on Ventilation in Premature Neonates

https://doi.org/10.21203/rs.3.rs-1004905/v1

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Neonates with apnea of prematurity (AOP) deteriorate clinically because CPAP often provides inadequate support during apnea. NAVA provides proportional ventilator support from the electrical activity of the diaphragm. When NAVA level is 0 cmH20/mcV (NN0), patients receive minimal support when breathing and backup ventilation when apneic. This study addresses feasibility of NN0 and time spent in back up ventilation. This was a prospective, two center, observational study of preterm neonates on NN0 for AOP. Ventilator data were downloaded for 24 hours. Number of Clinically Significant Events (CSEs) and switches to back up were collected. Statistics were paired t-test. There were twenty-eight subjects with gestational age of 25 + 1.8 weeks; study age 28 ± 23 days. Number of events were 4±4.39 per 24 hours. Subjects were on NN0 approximately 90% each minute, back-up mode 2.5±1.1 times/minute with 10.6±7.2% in back-up.

Conclusion: Preterm neonates on NAVA level 0 had few clinically significant events with minimal time in back up ventilation.

Pediatrics

Neurally adjusted ventilatory assist (NAVA)

premature neonates

apnea of prematurity (AOP)

continuous positive airway pressure (CPAP).

NN0 is a method of ventilation that can reduce the number of CSEs compared with nCPAP in premature neonates with apnea.

What is new:

NN0 in preterm neonates provides augmented CPAP during spontaneous ventilation and back up ventilation during times of apnea. There is minimal time spent in back up ventilation which avoids excessive non-invasive ventilation or intubation when failing CPAP due to AOP.

Premature neonates remain vulnerable to the physiologic consequences of apnea of prematurity (AOP). Periods of clinical deterioration characterized by bradycardia and desaturation, referred to as clinically significant events (CSE), are frequently encountered in the neonatal intensive care unit (NICU).¹ Caffeine citrate and continuous positive airway pressure (CPAP) are commonly used therapeutic modalities demonstrating significant benefit^{2, 3, 4}. Unfortunately for the smallest and most fragile premature neonates, increasing respiratory support may be required. Noninvasive respiratory strategies have shown promise, although for severe apnea, intubation and mechanical ventilation may be needed^{2, 3, 5}.

Neurally Adjusted Ventilatory Assist (NAVA) provides support in synchrony with the patient’s respiratory efforts based on the detected electrical activity of the diaphragm (Edi). The NAVA level is a proportionality factor that converts the Edi signal into a pressure above the positive end expiratory pressure (PEEP). It is delivered with the Servo-I/U ventilator (Getinge, Germany) with NAVA software. If no Edi signal is detected for a predetermined amount of time (apnea time), the ventilator switches into pressure control ventilation until the patient breathes spontaneously again⁶. If the NAVA level is set at 0 cmH20/mcV, the patient receives minimal synchronized support above baseline PEEP while breathing and backup ventilation when apneic.

A previous study demonstrated a statically significant reduction in CSE for premature neonates ventilated on non-invasive NAVA of 0 (NN0) versus CPAP via the RAM cannula¹. However, the mechanism for this improvement was not studied. The objective of this current study is to further evaluate NNO acting as CPAP with backup ventilation. Primary outcomes are the time in NAVA versus backup ventilation and delineating ventilator pressures and respiratory rates.

This was a prospective, two center, observational study of preterm subjects admitted to ProMedica Ebeid Children’s Hospital and Akron Children’s Hospital NICUs during the time period of 8/2019- 2/2020. Subjects were placed on NN0 for AOP at the treating provider’s discretion. IRB approval and informed consent was obtained. Ventilator data were downloaded after 24 hours of NN0. Each data point was the breath-to-breath data averaged over 1 minute so 1,440 data points were collected for each subject. Demographics and number of CSE were collected. CSE were defined as bradycardia (less than 80 beats/min or desaturation (less than 90%) lasting more than 10 seconds. CSE were collected retrospectively from the electronic health record, for the duration of data collection on NN0. Statistics were paired t-test.

Twenty-eight subjects on NN0 were enrolled. 40,320 data points (each data point = 1 averaged minute) were collected for the 28 subjects. All subjects had apnea of prematurity (AOP), were being treated with caffeine, and were on the RAM cannula nasal interface. Table 1 shows the demographics of subjects. Ventilator settings were NNO, apnea time of 2 sec (minimum rate of 30 breaths per minute), peak inspiratory pressure (PIP) limit of 35-40 cm H20, backup settings of PIP 19 ± 3.6 cmH20 and rate of 43 ± 5.48. Subjects were in NN0 approximately 90% of each minute (54 seconds), went into back-up ventilation mode 2.5±1.1 times per minute and spent 10.6±7.2% (about 6 seconds) of each minute in back-up mode (Figure 1). Total respiratory rate (RR) was 63.7±8.7 and was higher than the spontaneous RR which was 57.9±11 breaths per minute (p<0.001). Figure 2 shows the number of CSEs was 4±4.39 events per 24 hours. The mean airway pressure (MAP) was 9.1±0.8 cmH₂0 and was higher than the measured PEEP of 7.9±0.8 cmH₂0 (p<0.001). The average PIP of 10.9 ± 1.1 cmH₂0 was higher than MAP (p<0.001). The RAM nasal interface had a 91.9 ±4.5% leak with a mean supplemental oxygen requirement of 23.2±3.3%.

Table 1

Demographics of the study subjects. Ages and weights are average ± SD.
Number of subjects	28 (female 57%)
Gestational age (weeks)	25 ± 1.8 (range 23–29)
Birth weight (grams)	860 ± 257 (range 460–1100)
Median Apgar scores	5 (1 min), 8 (5 min)
Prenatal steroids	79%
Surfactant	92%
Age at study (days)	28 ± 23 (range 3-91)
Weight at study	1077 ± 375(range 405-2270)
IVH (grade III–IV)	0%
NEC	3.5%
ROP	14%
CLD	17%
IVH Intraventricular hemorrhage, NEC necrotizing enterocolitis, ROP retinopathy of prematurity, CLD chronic lung disease.

Expanded use of noninvasive ventilation strategies to decrease need for intubation and invasive ventilation remains a high priority. CPAP has remained the gold standard, although a significant percentage of preterm neonates will require escalation in respiratory support^{5, 7, 8}. Noninvasive respiratory support subsequently evolved with the provision of options such as NIPPPV (nasal intermittent positive pressure ventilation) to augment lung inflation and respiratory muscle unloading⁹. A flow triggered synchronized mode of NIPPV was also found to have beneficial effects on reducing apnea and desaturations as compared to CPAP and NIPPV¹⁰.

NAVA, a novel mode of ventilation, changed the paradigm by providing synchronized ventilation in which both the timing and degree of ventilatory assist are controlled by the patient. Several studies have demonstrated decreased PIPs, oxygen requirement and apnea in preterm neonates receiving NAVA ventilation compared to traditional SIMV, pressure control ventilation^{11, 12, 13}.

Compared to CPAP, NIV NAVA in neonates has been shown to reduce the need for intubation, to facilitate early extubation and decrease extubation failures^{9, 14, 15, 16}. NIV NAVA has also been shown to decrease the number of CSE when compared to nonsynchronous, noninvasive ventilation¹⁷.

NN0 is the only available non-invasive mode which delivers CPAP while breathing and backup ventilation when the patient is apneic. Utilizing NN0 as a strategy in neonates who have apnea on CPAP was recently studied and demonstrated significant benefit in reduction of CSE¹. This approach offers the advantage of reducing CSE while minimizing exposure to noninvasive ventilation.

When NIV NAVA is set at 0 cmH20/mcV, the Servo I/U delivers a PIP of 2 cmH20 above PEEP in synchrony with the patient’s spontaneous breaths¹. The NAVA software has patient interface resistance compensation and accounts for this small increased pressure observed above the PEEP. This minimally augmented pressure delivered with each breath translates into a higher overall mean airway pressure and may be responsible for the improvement noted in CSE in previous studies¹. Even though average set PIP delivered 19 cmH₂O with each breath, measured average PIP was only 10.9 cmH₂O. This was expected seeing that there were so few backup breaths each minute so that the average delivered PIP was decreased. Although the average PIP was higher than MAP it is unlikely that this additional pressure of less than 2 cmH₂0 (10.9 vs 9.1 cmH₂0) was providing any substantial ventilatory support, especially when taking the large leak (92%) at the nasal interface into consideration.

Our data demonstrate that the percentage of time preterm neonates spent in back up ventilation was quite low. Studies have shown improved patient ventilator synchrony with NAVA ventilation with a resultant decrease in the number of apneic events^{12, 17}. Although these studies attributed the decreased CSE to being on NIV NAVA, perhaps it is the additional breaths delivered during periods of apnea which contributed to decreasing the numbers of CSE. These additional backup breaths account for the total respiratory rate that is higher than the spontaneous respiratory rate (64 vs. 58 breaths per minute) but still remain well within the normal respiratory rate range for neonates. Using an apnea time of 2 seconds meant that all patients had a minimum rate of 30 breaths per minute. Despite this short apnea time, there were very few switches to back up pressure control ventilation and the percentage of time each minute spent in back up mode was also very low. This short apnea time may have prevented any extended periods of apnea and contributed to the improvement in CSE.

This study is limited by the inability to fully determine the mechanism of the reduction in CSE. To further explore these reasons for this reduction in CSE, prospective studies would be needed to compare CPAP with various levels of PEEP when on NN0.

NNO in preterm neonates acted as minimally augmented CPAP during spontaneous ventilation and provided backup ventilation when apneic. Increased MAP and total RR may explain why this mode was effective. Despite the large leak, the RAM nasal interface was effective at delivering CPAP (NN0) with backup ventilation. This modality may offer a safe and effective option to avoid excessive non-invasive ventilation or intubation in premature neonates failing CPAP due to frequent CSEs.

AOP Apnea of prematurity

CPAP Continuous positive airway pressure

CSE Clinically significant events

Edi Electrical activity of the diaphragm

NAVA Neurally adjusted ventilatory assist

NIPPV Non-invasive positive pressure ventilation

NIV NAVA Non-invasive NAVA

NN0 Non-invasive NAVA of 0

PIP Peak inspiratory pressure

Funding: No funding received for this study.

Conflicts of Interest/Competing Interests: HS and KF are on the speakers’ bureau for Getinge and Chiesi USA Inc. AP, SH, and DL have nothing to disclose.

Availability of data and material: N/A

Code Availability: N/A

Authors Contributions: AP, KF, and HS contributed to the study design. AP, KF, SH, DL, and HS contributed to the 112 data collection, and all authors contributed in writing the manuscript.

Ethics Approval: Approved by Promedica and Akron Children’s Hospital IRBs.

Consent to Participate: Informed consent was obtained from the parents of participants of this study.

Consent for Publication: All authors give consent to publish.

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The Effect of NIV NAVA 0 on Ventilation in Premature Neonates

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