Reference values for diaphragm electrical activity (Edi) in newborn infants

The initiation of a spontaneous breath by the respiratory centre of the brain results in the electrical excitation of the diaphragm via the phrenic nerve and subsequent diaphragmatic contraction to facilitate an inflow of air. Recently, new technology has become available that can measure diaphragmatic excitation and associated electrical activity of the diaphragm (Edi) [1]. This is achieved using an Edi catheter, which is a specialised naso/orogastric tube that has electrodes embedded at the level of the gastro-oesophageal junction. The catheter assesses neural respiratory control by measuring the total action potentials of the motor units in the diaphragmatic crura [1], representative of phrenic nerve activity and global diaphragm activation [2]. The Edi is presented as a waveform with a cyclic pattern that has distinctive peak and minimum values. There are two key measures from this Edi waveform: (1) Edi minimum (the end expiratory Edi value [just prior to the subsequent inspiration]); and (2) Edi peak (the amplitude of electrical activity associated with inspiratory effort) [3].

These Edi waveforms can be filtered, processed and relayed to a ventilator, which can then provide synchronised inspiratory pressure support. The ventilator provides support that is proportional to inspiratory effort, based on the difference between the Edi peak and Edi minimum. This modality, referred to as neurally adjusted ventilatory assist (NAVA), is an emerging mode of respiratory support that can be utilised either non-invasively via nasal prongs or mask, or invasively [4]. Over 100 clinical and experimental studies have demonstrated the benefit of neural monitoring and ventilator assist control compared to conventional modes of ventilation, during both non-invasive and invasive ventilation. These studies have shown that NAVA improves patient-ventilator interaction, offering equivalent or improved physiological outcomes and favourable ventilator parameters (lower peak inspiratory pressures and down-regulation of Edi to limit over-assist) [5, 6].

Although several studies have evaluated the clinical use of NAVA in newborn infants, reference Edi data in healthy neonates have previously only been collected in two studies, involving 20 infants [3, 7]. However, data pertaining to healthy preterm and term infants not requiring respiratory support is limited. Establishing reference values for this population is important for the clinical utility of this technology. Excessive respiratory support can suppress an infant’s natural respiratory drive while under supporting breathing is also detrimental [8]. The potential morbidity and mortality associated with incorrect support is well established [9].

This observational study of preterm and term newborn infants aimed to establish reference Edi values. We also sought to determine how these values vary according to sleeping states, feeding and skin-to-skin care.

The observational data in this study represent Edi waveforms from a large cohort of healthy preterm and term newborn infants, which we have used to define reference values for Edi minimum (1–5 μV) and Edi peak (3–17 μV). These values can be used as a reference in clinical practice to define a goal for electrical activity in infants requiring respiratory support. This is particularly relevant in infants being supported with NAVA as breathing support is always proportional to the infant’s Edi activity (specifically, proportional to the difference between the Edi peak and Edi minimum). There was no significant difference found between the preterm and term population in the study suggesting that diaphragm electrical activity is similar in infants that are spontaneously breathing without support. This supports the use of these reference values in both preterm and term infants.

We noted that diaphragm electrical activity was significantly higher when infants were awake. This is an expected finding as the sleep stage is characterised by slower, more regular respiration rates [10]. It is also consistent with previous studies, which demonstrated that peak Edi activity was 60% higher in the awake state [3]. Peak Edi was also significantly lower during skin-to-skin care, which has previously been reported and is not surprising given the known positive effects of skin-skin care on cardiorespiratory stability and sleep quality [11‐13]. It should be noted, however, that only three infants had skin-to-skin care during their respective observation periods.

We found no significant difference in Edi waveforms when comparing waveforms before and after feeds. This is consistent with previous studies investigating changes in Edi with naso/orogastric feeds [14]. There are other studies that have shown a post-prandial decrease in peak Edi, however, this was in a small population of term infants who were suck feeding [3]. The majority of infants in this study were predominantly fed with a naso/orogastric tube, which is likely to explain the discrepancy.

It is important to recognise that the Edi waveform is variable in individual infants. Infants often have irregular, periodic breathing patterns that can fluctuate with time. The effects of clinical variables such as sigh breaths, apnoeas, use of accessory muscles and changing respiratory rate are not reflected when the Edi waveform is averaged. When using reference ranges, the trend in an individual infant’s Edi waveform is more important than any single value. There is also variability between infants, which explains why there is an overlap between the reference ranges for Edi minimum and Edi peak (it is not possible for the Edi minimum to be greater than the Edi peak at any one point in time).

There were some important limitations to acknowledge with respect to this study. Although these data represent the largest reported cohort of spontaneously breathing preterm and term infants, the sample size does not allow for a true reference range based on gestation. We found that the electrical diaphragm activity is similar in preterm infants and term infants, but these were all infants who did not require respiratory support. This reflects an increasingly small percentage of the population as gestation decreases. Consequently, we were not able to recruit infants less than 29 weeks gestation where differences in diaphragm activity may be more apparent. We also acknowledge that the inclusion of infants admitted to a special care nursery may not represent a true healthy newborn population. Although infants were subjectively breathing comfortably at the time of enrolment, some residual subclinical respiratory disease cannot be ruled out. We are reassured that our findings are similar to previous published data [3, 5, 6]. Finally, it is important to note that Edi signals may be affected by equipment and software factors, such as electrode configuration or signal amplification. This again highlights the value of trend monitoring when interpreting Edi data in an individual infant.

In summary, reference Edi minimum and peak values were established for both preterm and term neonates. These values can be used as a guide for clinicians when using diaphragm-triggered modes on respiratory support in newborn infants to ensure an optimal level of respiratory support.