Work of breathing using high-flow nasal cannula in preterm infants

(), 7 8 r Nature Publishing Group All rights reserved. 73-83/ $3 www.nature.com/jp ORIGINAL ARTICLE Work of breathing using high-flow nasal cannula in preterm infants JG Saslow 1,, ZH Aghai 1,, TA Nakhla 1,, JJ Hart 1, R Lawrysh 1, GE Stahl 1, and KH Pyon 1, 1 Department of Pediatrics, Division of Neonatology, The Children s Regional Hospital at Cooper University Hospital, Camden, NJ, USA and Department of Pediatrics, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Camden, NJ, USA Objective: To compare the work of breathing (WOB) in premature neonates supported with high-flow nasal cannula (HFNC) and nasal continuous positive airway pressure (NCPAP). Study Design: Eighteen preterm neonates <. kg on HFNC or NCPAP support were studied in a random order. A ventilator was used to deliver cmh O of NCPAP with nasal prongs. High-flow nasal cannula delivered with Vapotherm (VAPO) at 3, and 5 l/min was used. Tidal ventilation was obtained using respiratory inductance plethysmography calibrated with face-mask pneumotachography. An esophageal balloon estimated pleural pressure from which changes in end distending pressure were calculated. Inspiratory, elastic and resistive WOB and respiratory parameters were calculated. Results: No differences were found in the WOB for all settings. Changes in end distending pressure did not vary significantly over all device settings except VAPO at 5 l/min. Conclusion: In these preterm infants with mild respiratory illness, HFNC provided support comparable to NCPAP. (), 7 8. doi:1.138/sj.jp.71153; published online 11 May Keywords: high-flow nasal cannula; Vapotherm; work of breathing; nasal continuous positive airway pressure Introduction Newborns with respiratory distress have been treated with supplemental oxygen for decades. Nasal continuous airway pressure (NCPAP) is used to support those infants with mild-tomoderate respiratory distress syndrome (RDS), those who have been extubated after treatment for RDS, those experiencing apnea of prematurity and those with other forms of respiratory distress Correspondence: Dr JG Saslow, Division of Neonatology, Department of Pediatrics, Cooper University Hospital, 1 Cooper Plaza, Dorrance 75, Camden, NJ 813, USA. E-mail: saslow-judy@cooperhealth.edu Received February ; revised 11 April ; accepted 1 April ; published online 11 May soon after birth. 1 Its success has been attributed not only to respiratory support without the need for intubation but also prevention of reintubation. 3 Recently, the Vapotherm i device (VAPO; Vapotherm Inc., Stevensville, MD) was introduced as a high-flow nasal cannula system (HFNC) with high humidity, providing respiratory support to neonates. Vapotherm delivers higher flow rates with increased comfort to the patient. Although there are some published reports of VAPO use in adults, few studies have been conducted in premature infants. Observational studies and anecdotal reports on small numbers of premature infants have suggested the safety of VAPO 5 and effective transition from the ventilator to VAPO, with the existence of limited data. There has been increased use of VAPO in nurseries presumably because of anecdotal reports and experience that it is easy to use, and well tolerated by the infants, while experiencing decreased nasal septum erosion. However, there are no published trials to date to support or refute these perceptions. Moreover, it is being used as an alternative to NCPAP treatment. Because of the paucity of pulmonary mechanics data in the preterm neonate on VAPO, there is again very little in the literature to support this increased use. The purpose of this study was to compare the work of breathing (WOB) in a group of premature infants treated with HFNC and NCPAP. Materials and methods The study was conducted in the 39-bed, level III NICU at Cooper University Hospital in Camden, New Jersey. The study was approved by the Institutional Review Board and signed informed consent was obtained from parent(s) or guardian(s) before the study. Preterm infants were eligible for the study if <. kg birth weight and medically stable although requiring NCPAP or HFNC support for mild RDS, chronic lung disease (CLD) and/or apnea of prematurity. The infants were studied on both devices applied in a random order (NCPAP or HFNC), while in a supine position,

Pressure (cmh O) 77 without sedation, and each infant served as their own control. Nasal continuous positive airway pressure was delivered by connecting Inca nasal prongs (Ackrad Laboratories, Cranford, NJ) to an infant Bird ventilator (VIASYS Healthcare Inc., Conshohocken, PA) set in CPAP mode. The largest prongs that fit the infant s nares without blanching the surrounding tissue were used. High-flow nasal cannula was delivered using the VAPO system, which is capable of providing flow rates of 1 to 8 l/min with a relative humidity of 1%. 7 Data were collected while on VAPO at 3, and 5 l/min (VAPO3, VAPO and VAPO5, respectively), and NCPAP at cm H O (NCPAP) after a stabilization time of approximately 5 mins at each level of flow/pressure. The breaths collected over the last 3 s at each of the levels were used for the analysis. A detailed description of the data acquisition, validation and analysis was reported previously. 8 1 Chest wall and abdominal movements were recorded (SomnoStar, Sensormedics Corp., Yorba Linda, CA) in direct current-coupled mode using respiratory inductance plethysmography (RIP) bands (Respibands Plus, Sensormedics Corp., Yorba Linda, CA) placed around the infant s rib cage (RC) and abdomen (ABD). Direct comparison of volume changes measured by face-mask pneumotachography (Hans Rudolph Inc., Kansas City, MO) was used for calibration of the RIP data. Using a linear combination of RC and ABD measurements to compute two calibration coefficients (k 1 and k ), RIP volumes were calculated (V T RIP ¼ k 1 RC þ k ABD). 9 Measurements of tidal esophageal pressure were used to approximate pleural pressures using an esophageal balloon catheter (Viasys Healthcare Inc., Palm Springs, CA). The esophageal balloon catheter was advanced into the esophagus to approximately the lower third of the tracheal length. Proper placement validation was carried out as described previously in detail. 8 11 Using the Biopac MP1 data acquisition system (Biopac Systems Inc., Santa Barbara, CA), data were sampled at 1 Hz and collected. Calibrated RIP data and transpulmonary pressure (P tp ) changes derived from the esophageal pressure data were used to determine the following respiratory parameters: tidal volume (V T, ml/kg), respiratory rate (RR), lung compliance (C L ), phase angle and end distending pressure. The increase in end distending pressure from baseline (no NCPAP, no HFNC) was determined at NCPAP and at each VAPO level. Furthermore, WOB components were calculated using V T RIP and P tp data as described previously, 8 11 according to the standard Campbell s diagram 1 as shown in Figure 1. As WOB is altered by patients variations in tidal volume amplitudes, standardization was done by normalizing WOB by V T. Because each infant was his/her own control, a pairwise comparison of the two modes of support was performed using a paired t-test. Data were compared between NCPAP at cm H O and VAPO at 3, and 5 l/min. P <.5 was considered to be statistically significant. 1 5 WOB insp = RWOB i + WOB elast RWOB = RWOB i + RWOB e RWOBi 1 Volume (ml) RWOB e WOB elast 3 Figure 1 Example for pressure volume (P V) loop used to illustrate work of breathing (WOB) components and method of WOB calculation according to the standard Campbell s diagram. WOB insp (equivalent to area subtended by inspiratory (or upper) limb of P V loop) is the algebraic sum of WOB elast and inspiratory resistive WOB (RWOB i ). Area within P V loop is equal to RWOB expended during both inspiration and expiration. WOB elast was estimated as the area subtended by the straight line connecting start and end inspiratory points. Table 1 Patient demographics (N ¼ 18) Mean±s.d. Range (median) Birth weight (g) 1118±18 58 199 (1) Gestational age (weeks) 8.±3. 35 (7) Study weight (g) 15±33 87 (117) Study age (days).1±5.3 1 7 (13) FiO.3±.13.1. (.) Results Eighteen preterm neonates were enrolled and studied on both VAPO and NCPAP. Patient demographics are shown in Table 1. Inspiratory, elastic and resistive WOB (WOB insp, WOB elast and RWOB) at all device settings are shown in Figure. No significant differences were found in WOB insp, WOB elast and RWOB between NCPAP cm H O and VAPO 3, and 5 l/min. Compliance and phase angle (Table ) were also similar on the VAPO and NCPAP settings. There was a trend of increased compliance with increasing VAPO flow but it was only statistically significant at VAPO of 5 l/min (P ¼.3). Furthermore, there were no differences in the tidal volume and respiratory rate between the VAPO and NCPAP devices (Table ). The increase in end distending pressure from baseline (no NCPAP, no HFNC) was also determined at each setting (Figure 3). The pressures did not vary significantly over all device settings except at VAPO5 (P ¼.3, for NCPAP cm H O compared to VAPO 5 l/min) and the mean increase in pressure from baseline was below cm H O.

78 Table Respiratory parameters (mean±s.d.) at both devices and varying settings Device setting WOB insp (cmh O/ml) RWOB (cmh O/ml) WOB elast (cmh O/ml) Compliance (ml kg 1 /cm H O) Tidal volume (ml/kg) NCPAP VAPO 3 VAPO Device Setting Respiratory rate (breaths/min) VAPO 5 Phase angle (deg) NCPAP.83±.9 3.53±1.9 8.3±3.3 35.±.3 VAPO3.8±. 3.15±1.3 71.3±..8±7.7 VAPO.89±. 3.8±1.35 8.9±1.9 5.±. VAPO5 1.3±.7* 3.1±1.31.9±3..5±35. Abbreviations: NCPAP, nasal continuous positive airway pressure at cm H O; VAPO, Vapotherm. *P ¼.3. Figure Work of breathing (WOB) parameters (WOB insp, WOB elast, RWOB) shown as mean±s.d. at all device settings. Discussion Nasal continuous positive airway pressure is used as an alternative to mechanical ventilation when possible, to treat mild RDS, as respiratory support after extubation, and in the management of Pressure (cmh O) 5 3 1 1.7±1. 1.±.95 1.±.99 1.3±.77 NCPAP VAPO 3 VAPO Device Settings apnea of prematurity. Nasal continuous positive airway pressure has been shown to increase functional residual capacity, improve oxygenation and decrease the rate of CLD. 13,1 The Vapotherm i is a respiratory therapy device that allows high-flow rates (up to 8 l/min in infants) of breathing gases to be delivered by a type of nasal cannula (NC), using patented membrane technology to warm and saturate the gas stream. 15 Despite the lack of large controlled trials, and only small case reports or anecdotal impressions available in the literature, VAPO has been used as an alternative to NCPAP with the assumption of comparable respiratory support. Lain et al. 1 reported that HFNC (5 to l/min), humidified gas delivered by using the VAPO device was well tolerated by adults and concluded that VAPO decreased respiratory rates, increased oxygen saturation, added small amounts of positive end expiratory pressure and may decrease WOB. However, little data are available on pulmonary mechanics in premature infants on HFNC. No significant increase in intrathoracic pressure was shown in an adult study, whereas maintenance of oxygen content was confirmed. 1 Safety of VAPO was suggested in premature infants using 1 to 3.5 l/min, preventing reintubation. 5 High-flow nasal cannula using VAPO was shown to be as effective as NCPAP in the treatment of RDS in 13 infants requiring respiratory support. 17 Sun reported 19 preterm infants using VAPO with flow rates of to 8 l/min without evidence of barotrauma, CPAP belly, nosocomial infection or nasal mucus plugging. At present, the literature does not contain any pulmonary mechanics data in premature infants treated with VAPO. Data are limited to small case reports describing safety and efficacy. Our study is the first of its kind to measure pulmonary mechanics on premature infants treated with HFNC using VAPO. These data show no significant difference in WOB when comparing NCPAP of cm * VAPO 5 Figure 3 Increase in end distending pressure from baseline at all settings for VAPO and NCPAP at cm H O. Box plot: the boundary of the box indicates the 5th and 75th percentiles, the line within the box marks the median value and the error bars indicate the 5th and 95th percentile confidence intervals. The mean±s.d. increase from baseline is given below each box data. *P ¼.3 for Vapotherm at 5 l/min.

79 H O to different flow rates of VAPO (3, and 5 l/min). Tidal volume and respiratory rate were not statistically different between the NCPAP and the VAPO. There was a trend of improved compliance with increasing VAPO flow, with significance at VAPO of 5 l/min, and a tendency towards asynchrony with VAPO. VAPO used at 3, and 5 l/min did not show significant differences for all the WOB data and other respiratory parameters. One might postulate that with increased flow, the infants would receive more support. We speculate that the lack of change in the WOB may reflect the relatively mild respiratory disease, and/or that the small increase in VAPO support (from 3 to 5 l/min) may not have been high enough to show significant differences. In this small heterogeneous study population of 18 babies, only ten had been on ventilatory support and nine had been treated with surfactant. Questions have been posed regarding the amount of pressure delivered by the HFNC amid concerns of overdistention and potential harm from pneumothoraces. Chang et al., 18 in a bench study, measured the temperature, pressure, resistance and humidity with changes in VAPO, NCPAP and NC. This group found significantly elevated delivered pressure with increased levels of VAPO flow (VAPO>NC>NCPAP). No data have been reported in the literature on the pressures delivered to premature infants treated with VAPO. In our study, the measured esophageal pressure was used to approximate the end distending pressure, which should reflect changes in lung volume. Locke et al. 19 and Sreenan et al., by using esophageal pressures, demonstrated measurable distending pressures when using NC flow. Our results showed the mean increase in end distending pressure at NCPAP, VAPO3, VAPO and VAPO5 to be 1.7±1., 1.±.95, 1.±.99 and 1.3±.77 cm H O, respectively (Figure 3). The wide distribution of the pressure data may be owing to the heterogeneity of the patient population and the demographics, as shown previously in other related studies reporting changes in lung volumes 1 and lung mechanics. 8 The changes in end distending pressures were only significant at VAPO5 when compared to NCPAP, and the distending pressures changed only minimally with increasing levels of VAPO. We speculate that this lack of change in pressure at increasing VAPO levels is dependent on the baseline compliance, the respiratory needs and the severity of the infant s respiratory illness. Locke et al. 19 determined that positive distending pressure is also affected by the interaction of the NC, gas flow rate and the anatomy of the infant s airway. Furthermore, in our study, the area of the VAPO NC was 5.7 mm, whereas the average area for the infants nostrils was 13. mm. This would account for leaks around the cannula that would result in minimal changes in the distending pressure and ease the safety concerns that have been posed by clinicians. At the present time, Vapotherm has instituted a voluntary recall of the Vapotherm i humidification devices in clinical use owing to colonization with Ralstonia species. The source of this contamination is unknown and still under investigation. This recall process has been undertaken in order to conduct high-level disinfection processes for potentially contaminated units and these results will be published in the Mortality and Morbidity Weekly Report. In conclusion, in the patients studied, there were no differences in the WOB, and no increase in end distending pressures when comparing NCPAP and HFNC. We speculate that HFNC using VAPO is providing support comparable to NCPAP for these infants with mild respiratory requirements. Our study evaluated only VAPO flow rates of 3, and 5 l/min. A larger study with higher flow rates needs to be undertaken, as VAPO of up to 8 l/min has been used in clinical practice. In our study, the data were collected over a short time period of VAPO support; therefore, additional research is necessary to study its long-term effects. Further large-scale, randomized outcome trials are also needed to evaluate this new therapy along with the effects of HFNC on duration of supplemental oxygen, length of hospital stay, rates of CLD, infection and complications of pneumothoraces. Until such time, HFNC should be used with caution. Acknowledgments This study was conducted at Cooper University Hospital. Equipment support was provided by Vapotherm Inc., Stevensville, Maryland. None of the authors received any goods or money from Vapotherm, or hold any stock in this company. This work was presented in part at the Society for Pediatric Research/Pediatric Academic Societies Meeting in Washington, DC, May 5. 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