Bi-level positive airway pressure (biPAP) for non-invasive respiratory support of foals

Respiratory insufficiency and pulmonary health are important considerations in equine neonatal care, as the majority of foals are bred for athletic function. The administration of supplementary oxygen is readily implemented in equine practice settings, but this does not address respiratory insufficiency due to inadequate ventilation and is no longer considered optimal care for hypoxia in some settings. Non-invasive ventilatory strategies including continuous or bi-level positive airway pressure are effective in human and veterinary studies, and may offer improved respiratory support in equine clinical practice. The current study was conducted in two parts to investigate the use of a commercial bilevel positive airway pressure (biPAP) ventilator, designed for home care of people with obstructive respiratory conditions, for respiratory support of foals. In Part 1 a prospective observational study was conducted to evaluate the effect of sequential application of supplementary oxygen and then biPAP for respiratory support of five foals ≤ 4 days of age hospitalised with respiratory in sufficiency (Group 1) and four healthy, sedated foals < 28 days of age (Group 2). In Part 2, biPAP and supplementary oxygen were administered to six healthy foals with pharmacologically induced respiratory insufficiency in a two sequence, two phase, cross-over study (Group 3). Non-invasive ventilation by biPAP improved gas exchange and mechanics of breathing (increased tidal volume, decreased respiratory rate and increased peak inspiratory flow) in foals, but modest hypercapnia was observed in healthy, sedated foals (Groups 2 and 3). Clinical cases (Group 1) appeared less likely to develop hypercapnia in response to treatment, however the response in individual foals was variable, and close monitoring is necessary. Clinical observations, pulse oximetry and CO2 monitoring of expired gases were of limited benefit in identification of foals responding inappropriately to biPAP, and improved methods to assess and monitor respiratory function are required in foals.


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Respiratory disease has long been recognised as of considerable economic importance in newborn 36 (2,3). Optimal respiratory support is highly desirable to optimise survival and preserve respiratory 37 function in animals bred largely for their athletic potential.

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The use of non-invasive ventilation (NIV) is now widely regarded as the most effective approach for 40 respiratory support of human neonates (4, 5), with continuous positive airway pressure (CPAP) shown 41 to reduce the number of preterm infants requiring admission to neonatal intensive care (6), and to 42 decrease the risk of bronchopulmonary dysplasia or death in neonates requiring respiratory support 43 (7). The technique involves the delivery of a constant positive (greater than atmospheric) pressure to 44 the airway and preserves spontaneous respiration. The physiological effects are complex and likely to 45 vary depending on the underlying pathology (8), but benefits have been attributed to increased 46 functional residual capacity, decreased work of breathing and reduced airway resistance (4). Previous studies have demonstrated that CPAP is associated with improved respiratory function in a number of 48 veterinary species (9-12). CPAP has recently been shown to improve gas exchange in healthy foals 49 with pharmacologically induced respiratory suppression (13), however hypercapnia was observed in 50 treated foals in this study, and has been observed previously in anaesthetised horses during CPAP (10, 51 11, 14).

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Bi-level positive airway pressure (biPAP) is also recognised for the management of respiratory 54 insufficiency in human neonates, and has recently demonstrated improved treatment outcomes in 55 preterm human neonates in comparison to CPAP (15,16). By using lower expiratory pressures, biPAP 56 promises improved expiratory function and is recommended for management of conditions 57 associated with hypercapnia, such as chronic obstructive airway disease or asthma (17)(18)(19). In human 58 patients with obstructive airway conditions, expiratory airflow limitations may cause increased PaCO 2 59 due to overdistension of alveoli and consequent increased alveolar dead space (20-23), an effect 60 which has been termed dynamic hyperinflation (24). Table 1: Foals available for inclusion in observational studies assessing non-invasive respiratory support. Group 1 foals were hospitalised for treatment of 111 multiple problems including respiratory insufficiency. Group 2 foals were healthy foals < 28 days of age. A number of foals (F2, F5, F6 and F8) were 112 evaluated on multiple occasions. Arterial blood gas (ABG) samples were obtained from all foals at baseline (ambient conditions, standing and/or 113 recumbent), following respiratory support with oxygen supplementation (O 2 supp) by nasal insufflation (F1) or mask and bi-level positive airway pressure 114 (biPAP) with (+O 2 ) or without oxygen supplementation. For Group 1 foals, oxygen flow was 4 L/min (F4), 5 L/min (F5, F5'), 6 L/min (F3)   following biPAP (all P<0.001, Figure 1); differences at other times were not significant. Results

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following supplementary O 2 administration were not significantly different to those obtained after 299 biPAP (P=1.000). Hypercapnia (PaCO 2 > 60 mHg) was observed for two foals (F8 and F9) following O 2 300 administration (60mmHg and 66 mmHg, respectively), and following biPAP on both occasions for F9 blood glucose treatment attributable to treatment were not observed (Supplementary Figure 3).

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Blood glucose concentrations increased across all sampling times (likely due to administration of 304 xylazine), with results at T3 (P=0.013) and T5 (P=0.008) significantly higher than at T0, as were results 305 during O 2 (P=0.008) and biPAP (P=0.016, data not shown). 306 307 Figure 1: Blood gas results for Group 3 foals. Sedation was associated with a significant decrease in 308 PaO 2 at T0 (P=0.002) and T1 (P=0.004). The administration of supplementary oxygen by mask (O 2 ) or 309 during bi-level positive airway pressure ventilation (biPAP) was associated with a significant increase 310 in PaO 2 at all other time points (all P<0.001), and results following biPAP were significantly greater 311 than following O 2 , as indicated. Results for arterial CO 2 pressures were not normally distributed, and 312 were resistant to transformation. Results at T-1 and T0 were significantly less than results following 313 O 2 and biPAP, as shown (**, P<0.001), following analysis by Kruskal Wallis test. Differences in PaCO 2 314 were not different following O 2 or biPAP (P=1.000). Data are shown as mean (+), median (horizontal 315 line) and quartiles (box), with whiskers and outliers determined by Tukey method. shown. The administration of biPAP was associated with greater O 2 extraction than observed at any 346 other time (**, all P<0.01). Oxygen extraction was also greater during mask O 2 administration, as 347 shown, and at T0 (standing foals following administration of diazepam) than at T3 (P=0.046) or T5 348 (P<0.001). The elimination of CO 2 was greatest at T0 than at any other time, except following biPAP 349 (*, all P<0.05). Differences between effects observed following biPAP administration and at other 350 times are shown. Data are shown as mean (+), median (horizontal line) and quartiles (box), with 351 whiskers and outliers determined by Tukey method.

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Significant effects were observed for both inspiratory and expiratory time, reflective of changes 354 observed in RRs (Figure 2), but there was no effect on I:E ratio (data not shown). Peak inspiratory flow 355 was greatest during biPAP (-1.52 L/s), and significant effects were observed compared to values 356 obtained at T1 (P=0.005) and T3 (P=0.037). Expiratory flows were greatest in unsedated foals (T-1), 357 and significant differences were observed at T1 (P=0.002), T3 (P=0.016) and during biPAP (P=0.003).

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Time and sequence effects were observed for data derived from analysis of inspired / expired gas 360 composition due to differences following O 2 administration or biPAP at T2 (Supplementary Figure S5). Paired results for pulse oximetry (SpO 2 ) and haemoglobin saturation determined by blood gas analysis 383 (sO 2 ) were available for 47 data sets from the current study. SpO 2 results correlated significantly with 384 sO 2 (r=0.61, 95% CI 0.34 to 0.78, P<0.001), but there was poor agreement between these two methods 385 of assessing haemoglobin saturation (Figure 3). Although bias was minimal (1.4%, standard deviation 386 5.4%), the observed limits of agreement were large (-11.95 to 9.2%), and increased divergence was 387 observed for results obtained from the most hypoxic foal. Paired results for CO 2 max and PaCO 2 were 388 available for 136 data sets (Figure 3). There was poor but significant correlation between results