The impact of different prong-nares ratio on ventilation in COPD patients using nasal high-flow (NHF) – a physiological study (2024)

Introduction

Nasal high flow (NHF) is a popular technique to provide support in respiratory failure in different conditions. Recently published bench studies have hypothesized that airway pressure can be increased by using different cannula sizes and corresponding prongs resulting in a range of prong-nare ratios. We conducted this study to verify these experimental findings in clinical practice.

Methods

We characterized prong size and flow rate dependent changes in ventilation parameters and changes in hypercapnia in an interventional clinical setting. Outcome parameters included changes in mean airway pressure, tidal volume (TV), respiratory rate (RR), minute volume (MV) and decrease in pCO₂. The ventilatory parameters were determined at 20, 30, 40 and 50l/min with 3 different prong sizes. 20 and 40l/min and the 3 different prong sizes were used to document the changes in pCO2.

Results

In this study we demonstrate changes in ventilation with increasing flow rates of NHF. A significant increase in mean airway pressure was seen with every 10l/min increase in flow rate. Respiratory rate and minute volume (using large prongs) changed significantly with larger increases in flow rate, while tidal volume was not significantly altered. When the flow rate was increased by 20l/min (i.e. from 20l/min to 40l/min) capillary pCO₂ decreased significantly. None of the measured values were significantly altered by the prong size used.

Conclusion

In summary, we presented strong indications that different prong sizes have no influence on essential respiratory parameters or the elimination of pCO₂ when using NHF in COPD patients.

Nasal high flow (NHF) is a popular technique to provide support in respiratory failure in different conditions. The mechanisms involved have been described in detail but are not yet fully understood [1]. NHF generates a small expiratory airway pressure with possibly associated with some recruitment of alveolar space, stabilizes oxygenation delivery by prevention of room air entrainment, increases the rate of carbon dioxide clearance during breathing, reduces dead space ventilation and improves breathing patterns [1]. The individual importance of these separate effects is presently unclear.

Nasal high flow is used in acutely hypoxemic patients in the majority of cases. The highest possible flow rate and large prongs are often used. However, this is not the best setting for every patient. It is known, for example, that the best tolerance in patients with chronic respiratory insufficiency is 30–35l/min, a flow rate that has been demonstrated to reduce the rate of acute exacerbations [2, 3]. However, an increase in flow rate leads to an increase in carbon dioxide clearance [4]. The same may result from increased leakage at nares, an effect that reduces hypercapnia in an animal model [5]. In a study from Bräunlich et al. in adults both increasing flow rate and removing a prong from one nare was effective and led to a decrease of capillary pCO2 level [6]. Crimi et al. showed that the rate of exacerbations in bronchiectasis patients was reduced by using NHF [7]. This is likely due to humidification and warming of the airways. Humidification and warming may not require very high flow rates (median flow rate 33l/min; e.g. Crimi). With increasing experience in using NHF in various clinical settings it appears useful to define more targeted use cases for NHF. At the same time, it is still necessary to gain more insight into the various aspects and parameters influencing the effectiveness of NHF.

Recently published bench studies have hypothesized that airway pressure can be increased by using different cannula sizes and corresponding prongs resulting in a range of prong-nare ratios. In the studies by Pinkham et al. it was shown that higher airway pressure is generated by higher flow and by occluding a larger area of the nostrils, which can be achieved by increasing the size of the cannula. This could mean that oxygenation can be improved by using larger nasal prongs. On the other hand, using smaller prongs and thus increasing the leakage may lead to improved CO2 washout. This conclusion seems logical but has so far been proven in model studies [8, 9]. Only the study by Zhao et al. has so far reported an increase in airway pressure when using the NHF in humans. In this study, however, only healthy sample ends were measured and the airway pressure in the nasal vestibule (4cm depth of the measuring catheter) was determined [10].

We conducted this study to verify these experimental findings in clinical practice. We tested whether different prong sizes might have an influence on airway pressures and pCO2 levels during NHF support of ventilation.

We characterized prong size and flow rate dependent changes in ventilation parameters and changes in hypercapnia in an interventional clinical setting. Outcome parameters included changes in mean airway pressure, tidal volume (TV), respiratory rate (RR), minute volume (MV) and decrease in pCO₂. The ventilatory parameters were determined at 20, 30, 40 and 50l/min with 3 different prong sizes. 20 and 40l/min and the 3 different prong sizes were used to document the changes in pCO2 (Fig.1).

Subjects

We recruited 25 hypercapnic patients with chronic obstructive pulmonary disease (COPD) from the inpatient area of Leipzig University Hospital in 2015/2016. The study was approved by the local ethics committee and the patients gave their written consent to participate after receiving detailed information (ethics committee of the University of Leipzig, №. 414-14-06102014) and were registered (ClinicalTrials NCT02504814, first posted 22.07.2015). Inclusion criteria were stable COPD, age > 18 years and the ability to understand and follow the study procedures. Exclusion criteria were acute illness or other causes of respiratory limitation.

Device

In this study, we used the TNI softflow 50 device (TNI medical AG, Würzburg, Germany). The flow was applied with small (s), medium (m) and large (l) nasal prongs (TNI medical AG). This device was modified so that it was possible to apply 50l/min via a small nasal cannula. The correctness of the flow was checked with a flowmeter. The prong sizes were as follows (ID = inner diameter/ OD = outer diameter): small size (s) ID 3.2mm, OD 4mm, medium size (m): ID 3.9mm, OD 4.9mm large size (l): ID 5mm, OD 6mm.

Measurement of mean airway pressure

A flexible tube filled with water (inner diameter 1mm, original Perfusor^® cable type Standard, B.Braun, Melsungen, Germany) placed in the nasopharynx served as a pressure transducer. A pressure transducer (GMH3111, Greisinger electronic GmbH, Regenstauf, Germany) and a laptop were used to record the signal. Ten breaths were recorded during spontaneous breathing.

Measurement of tidal volume and respiratory rate

Sensor belts and a polysomnograph (Respitrace; CareFusion GmbH, Höchberg, Germany) were used to measure the TV. Patients were measured in a sitting position. The elastic sensor belts were placed 10cm below the jugular fossa and 10cm below the xiphoid process, and TV measurements were performed. We then calibrated the device individually for each patient, starting with a “normal” tidal breathing recorded with a standard pulmonary function device (Master Screen Body; CareFusion GmbH). By measuring the TV of ten breaths and simultaneously recording the sensor signal, we were able to calibrate the sensor belt signal to changes in lung volume. After calibration, volume measurements were performed during NHF and spontaneous breathing. Chest and abdominal excursions were recorded and volumes were calculated. The measurements were performed with different prong sizes (s, m, l) and repeated 3 times per size and flow. After each measurement, the baseline was resumed. Breaks were allowed and the measurements could also be interrupted. The mean value was calculated from this. The minute volumes were subsequently calculated for VT and RR. The respiratory rate was measured for 1min after stabilisation.

Capillary blood gas analysis

Patients were treated with different flows (20l/min and 40l/min) and the 3 different prong sizes. Capillary blood gases were collected from the earlobe 10min after application of a hyperemia-inducing ointment (Finalgon^®; Boehringer Ingelheim, Ingelheim, Germany). Measurements were taken under constant oxygen saturation before and 2h after NHF breathing.

Statistics

Data were analyzed using Student’s t-test and linear regression analysis (Sigma Plot; Systat Software GmbH, Ekrath, Germany). A probability level for the null hypothesis (no difference) of 5% (P,0.05) was accepted as significant. Results were expressed as mean ± SD values. Changes from baseline were presented as percentages in the VT, MV and pCO2 figures. In the statistical analysis, the measurements were compared with the baseline value or other flow rates. The P-values were determined using the raw values.

Demographic data are shown in Table1. All 25 patients were able to complete the examinations.

1. a)

   General changes of mean airway pressure, tidal volume and respiratory rate compared to baseline.

The tests showed a significant increase in mean airway pressure and tidal volume (except for small prongs at 20l/min), a decrease in respiratory rate and a decrease in minute volume (Figs.2, 3, 4 and 5).

1. b)

   Changes of mean airway pressure, tidal volume and respiratory rate by increasing flow rates.

By increasing the flow rate by 10l/min (min 20 to max 50l/min), a significant increase in the mean airway pressure was achieved (Fig.2). An increase of 10l/min did not result in a significant decrease in respiratory rate compared to the next step (e.g. from 20 to 30l/min). However, there was a significant decrease in respiratory rate when comparing flow rates of 30 vs. 50l/min(Fig.3; Table2). Tidal volume did not change with increasing flow rates (Fig.4). The calculated respiratory minute volume only showed a significant change depending on flow rates (20l/min, vs. 50l/min) (Fig.5).

1. c)

   Changes of mean airway pressure, tidal volume and respiratory rate by different prong sizes.

The different prong sizes did not lead to any changes in airway pressure, respiratory rate, tidal volume or minute volume (Figs.2, 3, 4 and 5) (Table 2).

1. d)

   Capillary blood gas analysis.

In contrast to the other measurements, investigations looking at blood gas changes, were carried out at a flow rate of 20 and 40l/min. The higher flow rate was associated with a significantly greater drop in pCO2. No influence of prong size on blood gases were noted (Table3; Fig.6).

In this study we demonstrate changes in ventilation with increasing flow rates of NHF. A significant increase in mean airway pressure was seen with every 10l/min increase in flow rate. Respiratory rate and minute volume (using large prongs) changed significantly with larger increases in flow rate, while tidal volume was not significantly altered. When the flow rate was increased by 20l/min (i.e. from 20l/min to 40l/min) capillary pCO₂ decreased significantly. None of the measured values were significantly altered by the prong size used.

In our investigations, we also found the known results when using NHF in COPD patients [4]. However, ventilation changes with increases in flow were only visible with large flow differences in respiratory rate and minute volume. Compared to breathing with low-flow oxygen, there was an increase in mean airway pressure, an increase in tidal volume, a decrease in respiratory rate and a decrease in minute volume. In the case of our patients with respiratory muscle pump failure, these effects are easy to explain: in hypercapnic patients, muscle pump failure leads to a reduction in alveolar ventilation and dead space ventilation increases. By introducing a breathing volume by means of the NHF flow, the patient no longer has to do part of the work to overcome the physiological dead space. This means that muscle strength can be used to improve alveolar ventilation. This leads to the observed increase in tidal volume, the drop in respiratory rate and a decrease in respiratory minute volume. This activation of breathing and the increase in alveolar ventilation leads to increased elimination of pCO2. The wash-out is another effect that contributes to lowering the pCO2. As a result, the CO2 is increasingly washed out or less rebreathed by the flow, leading to a decrease in endobronchial CO2 and thus to a decrease in pCO2 in the blood [5, 6]. This effect can also be intensified in our study by increasing the flow rate.

However, the physiological effects of NHF are numerous and in some cases insufficiently understood and can also influence the changes found. Initially, NHF was predominantly viewed as a pressure-generating system [11]. Studies that showed a recruitment of lung areas concluded that a pressure increase in the airways was the decisive mechanism of the NHF [12, 13]. The conclusion was that the improvement in oxygenation was due to the recruitment of lung areas. However, physiological studies have shown that alveolar recruitment is much lower with NHF compared to a closed respiratory support system.

It was since assumed that other mechanisms were also involved in the observed improvement in oxygenation. Hypoxemic respiratory insufficiency are regularly accompanied by an increase in tidal volume and respiratory rate i.e. an increase in ventilation. In this case, inspiratory flow rate may reach up higher. Low flow oxygen supply is greatly diluted by inhaled room air and inspired oxygen concentrations will be unintentionally low.

NHF instead provides high flow rates of the intended oxygen air mixture. CO2 Wash out of the upper airways and refilling it with the intended oxygen/air mix makes ventilation more effective and reduces dead space of the airways and consequently reduces the need for ventilation.

These effects of NHF led to the theory that improved sealing of the airway might improve oxygenation and CO2 wash out. Following this idea, Pinkham et al. published two studies showing that NHF breathing led to an increase in airway pressure in a flow- and prong-size dependent manner. Air leaks around the prongs were reduced by choosing larger prong sizes. Both studies however used a pure model system [8, 9].

The many subtle differences between models, volunteers and COPD patients may help to explain, why in this study we could not confirm an influence of prong size on various ventilation parameters in COPD patients: it is easy to imagine that the walls of the airways in a model differ from those in a COPD patient in terms of elasticity; in obese or severely overinflated patients, a small increase in airway pressure may not suffice to alter recruitment; patients in respiratory distress will not always keep their mouth closed. In addition, nostrils in patients are more or less compliant and not of round shape. All of these effects may contribute to the lesser importance of prong size in patients as compared to prong size in models and volunteers.

The CO2 washout effect during NHF use has repeatedly been described [4, 5, 14,15,16]. This effect includes washing out expired gas the remains in the upper airways prior to the next breath. This has been visualized and quantified using krypton gas e.g. by Möller et al. It should be noted that no breathing took place during the washout process in this study. We found indications (in another model study) that the airways distal to the epiglottis may also be washed out to some extent even in the absence of respiratory movements. Studies in patients have demonstrated pCO₂ decreases in trachea and in capillary blood [16,17,18].

Based on the data of Frizzola et al., the question arises as to whether the effect of CO₂ washout can be increased by increasing nasal and/or oral leakage. Frizzola et al. showed in the piglet model that an improved CO2 removal can be achieved by increasing the leakage by using different prong sizes or unilateral vs. bilateral prongs [5]. We have previously compared unilateral vs. bilateral prongs (unaltered flow chosen at the turbine) in humans and observed improved CO2 removal with increased leakage and unilateral NHF application [6]. However increased leakage was not measured but presumed and a higher flow in the remaining prong may have participated in this effect.

Pinkham et al. also examined the influence of prong size on CO2 elimination in their model study and concluded that a change in prong size did not alter CO₂ removal. In Frizzola`s study piglets were used and the smaller piglet lungs and relatively large piglet nostrils may have made up for a larger effect.

Our studies do not merely serve to complete an academic debate. They have a direct clinical impact on the use of the NHF. In clinical practice, it can be observed time and again that high flows are applied to all patients and that larger prongs must be used. However, this does not do justice to the differentiated use of the NHF. The choice of prong size and the associated objective determines the success of the treatment. For example, the idea of generating improved airway pressure with a strong occlusion of the nose can lead to a minimization of leakage. In hypercapnic patients in particular, this could lead to a reduction in CO₂ washout when using large prongs without an improvement in airway pressure.

Other parameters of NHF should also be investigated further, such as temperature and moisture that seem too much for some and not enough for other patients. To what extent are they associated to success or failure in acute or in long term treatment applications?

Many detailed questions still need to be clarified. As simple as NHF may appear to be with regard to its application, the conditions of it being successful are likely to be more complex.

Our study has limitations. First, due to the special group of hypercapnic COPD patients, our results cannot be generalized. Patients with no pulmonary disease with hypoxemic respiratory insufficiency, may show a different behavior. Second, our measurements were not performed under precisely defined conditions. As mentioned above, prong size to nostril size was not monitored. The patients were instructed to keep their mouths closed. However, small leaks cannot be ruled out with certainty. Both might have influenced the results. It is possible that the previous experiments in the model or in patients did not analyse the outcome parameters that describe the effectiveness of using different sized prongs. Here it would be necessary to examine further outcome parameters. Thirdly, the effects may be different when using other prongs or prongs-nare differences.

In summary, we presented strong indications that different prong sizes have no influence on essential respiratory parameters or the elimination of pCO₂ when using NHF in COPD patients.

NHF:

Nasal high-flow

COPD:

Chronic obstructive pulmonary disease

NIV:

Non-invasive ventilation

Authors and Affiliations

1. Department of Respiratory Medicine, University of Leipzig, Liebigstrasse 20, 04103, Leipzig, Germany

   Jens Bräunlich&Hubert Wirtz

2. Department of Respiratory Medicine, Emden Hospital, Bolardusstrasse 20, 26721, Emden, Germany

   Jens Bräunlich

Contributions

All authors were involved in every stage of the study and manuscript preparation.

Corresponding author

Correspondence to Jens Bräunlich.

Ethics approval and consent to participate

The study was approved by the local ethics committee and patients gave their informed consent to participate (ethics committee of the University of Leipzig, №. 414-14-06102014, ClinicalTrials NCT02504814, first posted 22.07.2015.

Consent for publication

Not applicable.

Competing interests

JB and HW received travel grants, accommodation fees, device and study support by TNI medical AG.

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