Effect of expiratory positive airway pressure on tidal volume during non-invasive ventilation

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1 Original Paper Effect of expiratory positive airway pressure on tidal volume during non-invasive ventilation Chronic Respiratory Disease 2017, Vol. 14(2) ª The Author(s) 2016 Reprints and permission: sagepub.co.uk/journalspermissions.nav DOI: / journals.sagepub.com/home/crd W Kinnear, L Watson, P Smith, L Johnson, S Burrows, J Colt, M Sovani and A Khanna Abstract During non-invasive ventilation (NIV), tidal volume (V t ) will depend upon the difference between inspiratory and expiratory positive airway pressure (IPAP and EPAP, respectively), provided the respiratory muscles are relaxed and the lungs and chest wall therefore move along their passive pressure volume curves. To test this hypothesis, we studied the effect of increasing EPAP during pressure-controlled modes of NIV in 30 long-term ventilator users (10 each with scoliosis, obesity hypoventilation or neuromuscular disorders). While maintaining the same IPAP, addition of 5 cmh 2 O of EPAP reduced mean V t by 167 ml; 10 cmh 2 O reduced V t by 367 ml. This pattern was seen in all three patient groups. EPAP has several potential advantages, for example maintaining upper airway patency, preventing basal atelectasis and facilitating triggering. EPAP does, however, appear to reduce V t. Decreasing EPAP is an alternative to increasing IPAP if measurements of gas exchange during NIV indicate that ventilation is inadequate. Keywords Non-invasive ventilation, respiratory muscles, scoliosis, ventilation, respiratory failure Introduction Non-invasive ventilation (NIV) is used widely in the treatment of respiratory failure. It involves the application of positive pressure to the airway using a mask placed over the nose or mouth as the interface between the ventilator and the patient. In the early days of NIV, inspiratory positive airway pressure (IPAP) was used without any positive pressure during expiration (expiratory positive airway pressure (EPAP)). In order to avoid rebreathing of exhaled air, a valve which opened during expiration was placed at the patient end of the circuit, or two separate ventilator tubes were used for inspiration and expiration. Almost all modern NIV ventilators incorporate EPAP as standard, since this allows a much simpler circuit to be used, withanexpiratoryport (rather than a valve) through which air leaks during both inspiration and expiration. EPAP also makes it easier for patients with chronic obstructive pulmonary disease (COPD) to trigger the ventilator, maintains upper airway patency and prevents basal atelectasis. EPAP may, however, impair the effectiveness of NIV. Provided the patient s respiratory muscles are relaxed, as they generally will be in long-term ventilator users using controlled modes of NIV, the tidal volume (V t ) achieved will depend upon the difference between IPAP and EPAP (called the driving-pressure or DP, sometimes also referred to as pressure support, pressure assist or span) and the compliance of the respiratory system (Crs). Increasing EPAP without changing IPAP will self-evidently reduce DP and hence V t, but the published literature on the extent of this effect is surprisingly sparse. Crs is an index of the combined elasticity of the lungs and chest wall. It is an assessment of the passive Gateway B, Nottingham NHS Treatment Centre, Queens Medical Centre, Nottingham, UK Corresponding author: W Kinnear, Gateway B, Nottingham NHS Treatment Centre, Queens Medical Centre Campus, Nottingham, NG7 2FT, UK. william.kinnear@circlenottingham.co.uk

2 106 Chronic Respiratory Disease 14(2) Lung volume (l) E Positive airway pressure (cmh 2 O) Figure 1. The passive pressure-volume curve of the respiratory system. Applying positive airway pressure increases lung volume by an amount which depends on the compliance of the respiratory system (Crs). Crs is traditionally taken as the slope of this line immediately above resting end-expiratory lung volume (indicated as 0 in this figure); I indicates the point reached at the end of inspiration during non-invasive ventilation (NIV); E is the expiratory position, which varies during NIV depending upon the expiratory positive airway pressure (EPAP). mechanics of the respiratory system, assuming complete relaxation of the respiratory muscles. Measurements have generally been made opportunistically on patients under general anaesthesia, Crs being taken as the linear slope of the pressure volume curve (Figure 1) immediately above resting endexpiratory lung volume (EELV). Ever since the early days of NIV, it has been observed that the activity of the respiratory muscles is greatly reduced or even absent during NIV. 1 We wondered if this effect could be exploited, obtain an estimate of Crs in awake subjects. Our overall aim was to assist clinicians in choosing NIV pressures which achieve the most effective ventilation. Methods We studied 30 long-term NIV users. Ten consecutive patients were recruited from three diagnostic groups: thoracic scoliosis, obesity hypoventilation syndrome and neuromuscular disorders. Patients with significant airflow obstruction on spirometry were excluded from the study. We told the patients we wished to study the effect on their breathing of different settings on their ventilators, to which all gave their informed consent. They were using NIPPY-3 Crs I ventilators (B&D Medical, Stratford upon Avon, UK) in pressure control modes. In order to maximize respiratory muscle relaxation, we used their own mask and usual IPAP, respiratory rate and inspiratory time. These ventilator settings had been set previously to normalize gas exchange, while maximizing patient comfort. The mean (standard deviation (SD)) IPAP, respiratory rate and inspiratory times were 25 (4.2) cmh 2 O, 18.5 (4.9) breaths per minute and 1.20 (0.03) seconds, respectively. There were no significant differences in these settings between the three groups. In random order, we used three different ventilator settings: (1) intermittent positive pressure ventilation (IPPV) pressure control mode without EPAP (using an exhalation valve in the circuit), (2) bi-level pressure control with EPAP of 5 cmh 2 O and (3) bi-level pressure control with EPAP of 10 cmh 2 O. After 5 minutes settling on each ventilator setting, we recorded V t for 10 breaths using a Wright respirometer (Inspire Medical, Hertford, UK) inserted into the NIV circuit between the patient and the expiratory port or valve. All patients had well-fitting masks, with no apparent leaks. V t measurements were made during expiration, when the pressure within the circuit was lowest, in order to reduce the chances that mask leakage would distort our results. No supplementary oxygen was used during the study. Crs was calculated as the decrease in V t between IPPV (with an EPAP of zero) and bi-level NIV with an EPAP of 5 cmh 2 O, expressed as milliliters per centimeter of water. We assumed that any reduction in V t with the addition of EPAP was caused by increasing EELV (point E in Figure 1). We maintained a constant IPAP (relative to atmospheric pressure rather than to EPAP), so that passive inflation of the respiratory system would reach the same end-inspiratory lung volume (indicated by point I in Figure 1). Ideal body weight (IBW) was calculated using arm to estimate height, in order to correct for the effect of scoliosis on height. 2,3 All results are expressed as mean (SD). Statistical comparisons were made using Wilcoxon signed-rank tests. Results The second column of Table 1 shows the V t achieved during IPPV, with EPAP ¼ 0, for each group. The third column shows the effect of 5 cmh 2 O of EPAP, with bi-level pressure control ventilation using the same IPAP as during IPPV. EPAP produced a

3 Kinnear et al. 107 Table 1. Tidal volumes (in ml) recorded during non-invasive ventilation at different levels of expiratory positive airway pressure. EPAP (cmh 2 O) 0 þ5 þ10 Neuromuscular Scoliosis Obesity Total (259) 557 (274) 377 (251) 722 (17) 571 (189) 430 (171) 1117 (239) 905 (246) 625 (253) 845 (294) 678 (281) 478 (166) EPAP: expiratory positive airway pressure; V t : tidal volume; SD: standard deviation. OHS Scoliosis Neuromuscular IPPV EPAP 5 EPAP 10 Figure 2. V t during NIV with EPAP of zero, þ5 and þ10 cmh 2 O, expressed as a percentage of V t during IPPV with zero EPAP. V t : tidal volume; NIV: non-invasive ventilation; EPAP: expiratory positive airway pressure. reduction in V t in all subjects (p < 0.05), with a further fall when this was increased to 10 cmh 2 O, as shown in column 4 of Table 1. Figure 2 shows the mean V t for each group, expressed as a percentage of the value recorded without EPAP. For the whole group, mean V t was 10.8 ml/ kg IBW with IPPV, falling to 8.6 and 6.2 ml/kg with the addition of EPAP at 5 and 10 cmh 2 O, respectively. Mean Crs values were 28 ml/cmh 2 O for neuromuscular patients, 30 ml/cmh 2 O for scoliosis and 42 ml/cmh 2 O for obesity hypoventilation. Discussion We have shown that during NIV, the addition of EPAP leads to a reduction in V t. These changes were large as a proportion of V t, particularly with an EPAP of 10 cmh 2 O, implying that this level of EPAP significantly reduces ventilation. This detracts from the primary aim of NIV, which is to increase alveolar ventilation and correct hypercapnia. Faced with inadequate ventilation during NIV, clinicians will usually increase IPAP in order to produce a larger V t. While this is generally the correct strategy, our findings should act as a reminder that an increase in DP can also be achieved by reducing EPAP during bi-level NIV or switching to IPPV. The most common use of EPAP is to overcome upper airway obstruction in patients with the obesity hypoventilation syndrome. Within this syndrome, there is a spectrum of severity in terms of the mechanical effects of obesity, the contribution of upper airway obstruction and the impairment of central respiratory drive. In published studies, EPAP pressures titrated to overcome upper airway obstructiontendtobearound10cmh 2 O. 4 8 IPAP pressures are more variable, within the range cmh 2 O, probably reflecting the need for higher pressures in more severe obesity. With modern volume-assured modes of NIV, it has been noted that IPAP pressures tend to have to be increased in order to achieve an adequate V t, commonly targetedataround10ml/kgibw. 4,5,8 We suggest that 25 cmh 2 O is a reasonable IPAP pressure when commencing patients with obesity hypoventilation on pressure-controlled NIV. Combined with an EPAP of 10 cmh 2 O, the DP of 15 cmh 2 O should achieve a V t of around 8 ml/kg IBW. Persistent elevation of daytime arterial partial pressure of carbon dioxide (PaCO 2 ) or serum bicarbonate after commencing nocturnal NIV would suggest inadequate ventilation. While in some patients, this may reflect persisting upper airway obstruction, in our experience, it more commonly indicates an inadequate DP. This can be corrected by increasing IPAP, reducing EPAP or switching to IPPV. In published series, EPAP settings of less than 5 cmh 2 O are typically used in neuromuscular patients. 9,10 Our findings suggest that IPPV is the most suitable mode for this group or bi-level NIV with the lowest EPAP level which prevents rebreathing. Similar recommendations can probably also be extended to scoliosis. 11 NIV is generally used as a pressure-targeted mode of ventilation, on the grounds that leakage from the circuit and around mask produces an open system, compared to the closed conditions of a cuffed

4 108 Chronic Respiratory Disease 14(2) endotracheal or tracheostomy tube. Modern NIV ventilators are sufficiently sophisticated to produce estimates of V t. Our measurements suggest that pressure control modes of NIV, while not usually targeted to a specific volume, achieve V t consistent with those obtained during invasive ventilation. Similar values of ml/kg were seen in patients with neuromuscular diseases or scoliosis using NIV in a volumetargeted mode. 12 It could be argued that the decrease in V t with EPAP can simply be offset by increasing IPAP, but the curvilinear shape of the pressure volume curve of the respiratory system (Figure 1) means that the increase in IPAP will need to be larger in order to restore V t. Moreover, use of EPAP produces a higher mean airway pressure, which is at odds with the trend in invasive ventilation to use lower mean airway pressures, limiting V t to around 8 10 ml/kg IBW. For clinicians choosing NIV pressures for patients similar to those in our study, a Crs of 30 ml/cmh 2 O (or 40 ml/cmh 2 O for obesity hypoventilation) can be used as a guide to the V t which will be obtained for any given range of DP. For example, a patient with an IBW of 75 kg for whom a V t of 750 ml (10 ml/kg IBW) is required would need a DP of 25 cmh 2 O (750/30). For our study, we chose 30 long-term NIV users, on the grounds that they were all well used to NIV and, therefore, likely to relax their respiratory muscles during NIV. This allowed ustostudythepassive mechanics of their respiratory system. Cessation of respiratory muscle activity has been a consistent observation in studies of NIV. Previous work, looking at the relationship between IPAP and V t to estimate Crs, used electromyography (EMG) to confirm respiratory muscle relaxation in normal subjects who were not accustomed to NIV. 13 Although we did not use EMG to confirm complete relaxation of the respiratory muscles, we were employing an untriggered mode of NIV in experienced ventilator users. We feel that it is reasonable to assume that our estimates of Crs are not distorted by respiratory muscle contraction. Normal values for Crs obtained using the weighted spirometer were in the region of 100 ml/ cmh 2 O, 14,15 with similar values being observed during NIV. 13 For our patients with thoracic scoliosis, Crs values one-third of normal are consistent with previous work. 16 While it might seem surprising that respiratory muscle weakness is associated with similarly low Crs, reduced chest wall 17 and lung 18 compliance have been observed previously, probably reflecting chronic underinflation. It is important for clinicians treating such patients to be aware that Crs values are likely to be low, unlike the situation with acute neuromuscular problems. Morbid obesity is associated with low Crs, and again our values are consistent with previous studies. 19 Patients were in a stable clinical condition at the time of the study. Our findings may not apply to acute respiratory failure, when patients are less likely to completely relax their respiratory muscles and may have greater ventilation perfusion imbalance. We did not assess gas exchange in our study and were therefore unable to subdivide overall ventilation into dead space and alveolar ventilation. It is possible that EPAP reduces dead space, thus mitigating its effect on overall ventilation. In anaesthetized obese subjects, EPAP can increase V t by recruiting areas of collapsed lung. 20 This appears not to be the case even in our patients, possibly because we studied them while awake, or alternatively the use of NIV long term may have prevented atelectasis. Further studies during sleep are needed to see if the reduction in V t by EPAP is offset by its effect on upper airway patency. Higher levels of DP are associated with poor outcomes in the acute respiratory distress syndrome. 21 While clinical experience suggests that this is not the case in patients with chest wall problems such as those included in our study, this possibility also warrants further investigation in the context of NIV. We did not include patients with COPD in our study, as we have only a small number of such patients established on long-term NIV. Our findings cannot be extrapolated to this group, in whom EPAP may have additional effects in overcoming the effects of intrinsic positive end-expiratory pressure. Use of EPAP during NIV is becoming ubiquitous. This may be because it allows the use of simpler ventilators and circuits. EPAP is widely used in intensive care to prevent atelectasis. Physicians caring for long-term NIV users are likely to have large numbers of patients with obstructive sleep apnoea who use continuous positive airway pressure to maintain upper airway patency during sleep. While it is not unreasonable to expect EPAP to have similar beneficial effects in long-term NIV users, we feel that the detrimental reduction in V t may easily be overlooked. In our experience, many patients find IPPV without EPAP the most comfortable mode of NIV for long-term use. We encourage the use of this mode as the most effective way to increase ventilation and urge manufacturers to preserve it as an option on home ventilators.

5 Kinnear et al. 109 Declaration of conflicting interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. Funding The author(s) received no financial support for the research, authorship, and/or publication of this article. References 1. Ellis E, Bye PTP, Bruderer JW, et al. Treatment of respiratory failure during sleep in patients with neuromuscular disease: positive-pressure ventilation through a nose mask. Am Rev Respir Dis 1987; 135: Robinson JD, Lupkiewicz SM, Palenik L, et al. Determination of ideal body weight for drug dosage calculations. Am J Hosp Pharm 1983; 40: Hepper NGG, Black LF and Fowler WS. Relationship of lung volume to height and arm span in normal subjects and in patients with spinal deformity. Am Rev Respir Dis 1965; 91: Murphy PB, Davidson C, Hind MD, et al. Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomized controlled trial. Thorax 2012; 67: Masa JF, Corral J, Alonso ML, et al. Efficacy of different treatment alternatives for obesity hypoventilation syndrome. Am J Resp Crit Care Med 2015; 192: Piper AJ, Wang D, Yee BJ, et al. Randomised trial of CPAP vs bilevel support in the treatment of obesity hypoventilation syndrome without severe nocturnal desaturation. Thorax 2008; 63: Borel JC, Tamiser R, Gonzalez-Bermejo J, et al. Noninvasive ventilation in mild obesity hypoventilation syndrome: a randomized controlled trial. Chest 2012; 141: Janssens J-P, Metzger M and Sforza E. Impact of volume targeting on efficacy of bi-level non-invasive ventilation and sleep in obesity-hypoventilation. Respir Med 2009; 103: Vrijsen B, Buyse B, Belge C, et al. Noninvasive ventilation improves sleep in amyotrophic lateral sclerosis: a prospective polysomnographic study. J Clin Sleep Med 2015; 11: Simonds AK, Ward S, Heather S, et al. Impact of nasal ventilation on survival in hypercapnic Duchenne muscular dystrophy. Thorax 1998; 53: Tuggey JM and Elliott MW. Randomised crossover study of pressure and volume non-invasive ventilation in chest wall deformity. Thorax 2005; 60: Munoz X, Crespo A, Marti S, et al. Comparative study of two different modes of noninvasive home mechanical ventilation in chronic respiratory failure. Respir Med 2006; 100: Azarian R, Lofaso F, Zerah F, et al. Assessment of the respiratory compliance in awake subjects using pressure support. Eur Resp J 1993; 8: Berger R and Burke NK. The effects of posture on total respiratory system compliance. Am Rev Respir Dis 1982; 125: Heaf PJD and Prime FJ. The compliance of the thorax in normal human subjects. Clin Sci 1956; 15: Conti G, Rocco M, Antonelli M, et al. Respiratory system mechanics in the early phase of acute respiratory failure due to severe kyphoscoliosis. Intensive Care Med 1997; 23: Estenne M, Heilporn A, Delhez L, et al. Chest wall stiffness in patients with chronic respiratory muscle weakness. Am Rev Respir Dis 1983; 128: Ibson GJ, Pride NB, Newsom Davis J and Loh LC. Pulmonary mechanics in patients with respiratory muscle weakness. Am Rev Respir Dis 1977; 115: Salihoglu T, Salihoglu Z, Zengin AK, et al. The impacts of super obesity versus morbid obesity on respiratory mechanics and simple hemodynamic parameters during bariatric surgery. Obes Surg 2013; 23: Tusman G, Groisman I, Fiolo FE, et al. Non-invasive monitoring of lung volume recruitment maneuvres in morbidly obese patients: the role of pulse oximetry and volumetric capnography. Anesth Anal 2014; 118: Amato MBP, Meade MO, Slutsky AS, et al. Driving pressure and survival in the acute respiratory distress syndrome. New Eng J Med 2015; 372:

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