Abstract
BACKGROUND: High-flow nasal cannula therapy (HFNC) is widely used for patients with acute respiratory failure. HFNC has a number of physiological effects. Although FIO2 is considered to be constant, because HFNC is an open system, FIO2 varies according to inspiratory flow, tidal volume (VT), and HFNC gas flow. We investigated the influence of HFNC gas flow and other respiratory parameters on FIO2 during HFNC.
METHODS: We evaluated an HFNC system and, for comparison, a conventional oxygen therapy system. The HFNC apparatus was composed of an air/oxygen blender, a heated humidifier, an inspiratory limb, and small, medium, and large nasal prongs. HFNC gas flow was set at 20, 40, and 60 L/min, and FIO2 was set at 0.3, 0.5, and 0.7. We measured FIO2 for 1-min intervals using an oxygen analyzer and extracted data for the final 3 breaths of each interval. Spontaneous breathing was simulated using a mechanical ventilator connected to the muscle compartment of a model lung. The lung compartment passively moved with the muscle compartment, thus inspiring ambient air via a ventilator limb. With a decelerating flow waveform, simulated VT was set at 300, 500, and 700 mL, breathing frequency at 10 and 20 breaths/min, and inspiratory time at 1.0 s.
RESULTS: With HFNC gas flow of 20 and 40 L/min, at all set FIO2 values, inspiratory oxygen concentration varied with VT (P < .001). As the set value for FIO2 increased, the difference between set FIO2 and measured FIO2 increased. Neither breathing frequency nor prong size influenced FIO2.
CONCLUSIONS: During HFNC with simulated spontaneous breathing, when HFNC gas flow was 60 L/min, measured FIO2 was similar to set FIO2 at 0.3 and 0.5, whereas at 0.7, as VT increased, measured FIO2 decreased slightly. However, at 20 or 40 L/min, changes in VT related with deviation from set FIO2.
Introduction
Oxygen therapy is the first-line treatment for patients with organ dysfunction.1 For therapy, nasal cannulas and face masks are popular means of low-flow oxygen delivery. Via nasal cannula, oxygen flow is usually 1–6 L/min, and with an oxygen mask, a maximum flow of 15 L/min can be obtained. Meanwhile, inspiratory flow of patients with acute hypoxemic respiratory failure varies from 30 to >120 L/min,2 and actual FIO2 depends on the patient's breathing pattern; consequently, FIO2 is usually lower than assumed.3
High-flow nasal cannula (HFNC) therapy has come into widespread use for patients with respiratory failure.4,5 An air/oxygen blender generates a flow of up to 60 L/min, and the gas is heated and humidified with an active humidifier and subsequently delivered through a limb with a heating wire and via wide-bore nasal prongs. The FIO2 of respiratory gas can be adjusted to between 0.21 and 1.0. Adequately heated and humidified high-flow gas delivers some physiological benefits as well as improving thoraco-abdominal synchrony6 and washout of carbon dioxide in nasopharyngeal dead space.7 High flow creates positive end-expiratory nasopharyngeal pressure8,9,10 and is more comfortable than other noninvasive ventilation and air-entrainment masks.10,11 Physicians can also have greater confidence in the actual FIO2 being delivered to the patient.12 FIO2 depends, however, on the relationship between patient inspiratory flow and HFNC gas flow.13 We carried out this bench study to evaluate FIO2 during HFNC with various spontaneous breathing patterns and with different prong sizes.
QUICK LOOK
Current knowledge
HFNC can deliver, via wide-bore nasal prongs, up to 60 L/min of heated and humidified medical gas to a patient. Beneficial effects of HFNC include warming and humidification of inspiratory gas, a great advantage over other modes of oxygen delivery; reduction of thoraco-abdominal asynchrony; washout of carbon dioxide in nasopharyngeal dead space; low levels of PEEP; and a reliable supply of FIO2.
What this paper contributes to our knowledge
With HFNC gas flow of 20 and 40 L/min, as VT increased, measured FIO2 was less than set FIO2. When HFNC gas flow was 60 L/min, measured FIO2 was similar to set FIO2. As set FIO2 increased, the difference between set FIO2 and measured FIO2 increased.
Methods
Experimental Apparatus
We compared 2 delivery systems: HFNC (Optiflow, Fisher & Paykel Healthcare, Auckland, New Zealand) and conventional nasal cannula (Hudson RCI Softech, Teleflex Japan, Tokyo, Japan). The HFNC incorporates an air/oxygen blender with flow meter (OA2060, San-You Technology, Saitama, Japan) and a heated humidifier (MR850, Fisher & Paykel Healthcare, Auckland, New Zealand). HFNC gas flow was set at 20, 40, and 60 L/min, and FIO2 was set at 0.3, 0.5 and 0.7. A conventional nasal cannula was directly connected to a flow meter (P311, 1–15 L/min, Gunma Koike, Gunma, Japan), and flow was set at 2, 4, and 6 L/min at FIO2 = 1.0. Flow from the flow meter of HFNC was measured with a pneumotachometer (4700 series, 0–160 L/min, Hans Rudolph, Inc, Shawnee, Kansas) connected to a differential pressure transducer (TP-602T, ±5 cm H2O, Nihon Kohden, Tokyo, Japan). FIO2 of HFNC gas was also confirmed by an oxygen analyzer (LZ100, San-You Technology).
To simulate adult external nares, we opened 2 holes in a polyvinyl chloride cylinder (internal diameter 8 mm, length 10 mm, external naris area 83 mm2). One side of the cylinder was closed, and the nasal prongs were inserted into these holes (Fig. 1). The external nares were connected to a TTL test lung (TTL model 1601, Michigan Instruments, Grand Rapids, Michigan) via a standard ventilator circuit (22-mm Smoothbore system, 1.6 m, Intersurgical, Berkshire, United Kingdom). HFNC nasal prongs of 3 sizes, small, medium, and large (OPT542, OPT544, and OPT546, Fisher & Paykel Healthcare), and a conventional Softech nasal cannula were tested. Ratio of the cannula area to the area of external naris was 0.4 with large, 0.28 with medium, 0.15 with small, and 0.17 with conventional nasal cannula.
The high flow nasal cannula (HFNC) system incorporated an air/O2 blender with a flow meter and a heated humidifier. For the HFNC protocols, nasal prongs were connected to the manufacturer's standard circuit. We made 2 holes in a polyvinyl chloride cylinder to simulate adult external nares. The external nares were connected to the TTL test lung via a standard ventilator circuit. Spontaneous breathing was simulated using a mechanical ventilator and TTL test lung. To simulate spontaneous breathing, the muscle and lung compartment of the test lung were connected; consequently, the mechanical ventilator inflated the muscle compartment, whereupon the lung compartment inspired, along with ambient air, medical gas delivered, in turn, via each of the HFNC prongs and a conventional low-flow cannula. To monitor VT delivered to the lung compartment, flow to the lung compartment was measured using a pneumotachometer with a differential pressure transducer. Inspired gas downstream of the external nares was measured using an oxygen analyzer.
Simulated Spontaneous Breathing
Spontaneous breathing was simulated using a mechanical ventilator (Puritan-Bennett 840, Covidien, Carlsbad, California) and the TTL test lung. The muscle and lung compartments of the test lung were connected. The Puritan-Bennett 840 inflated the muscle compartment, causing the lung compartment to passively inflate, thus inspiring, along with ambient air, medical gas delivered via the HFNC or conventional nasal cannula being tested. The ventilator was set in volume control with descending ramp flow waveform. One-way valves prevented mixing of inspired and expired gases. Compliance of the TTL test lung was 0.05 L/cm H2O, and resistance was 5 cm H2O/L/s. Protocols were carried out with tidal volumes (VT) of 300, 500, and 700 mL and breathing frequencies 10 and 20 breaths/min. Inspiratory time was set at 1 s with decelerating flow waveform, and it resulted in 33, 55, and 77 L/min of spontaneous breathing inspiratory peak flow.
Experimental Settings
Before experimental testing, a ventilator self-test was performed. HFNC creates PEEP and increases residual volume in the lung compartment. We measured the end-expiratory pressure of the lung compartment and kept the residual volume of the muscle compartment at the same level as the lung compartment by setting corresponding levels of PEEP on the Puritan-Bennett 840. Flow to the lung compartment was measured with a pneumotachometer (4700 series, 0–160 L/min, Hans Rudolph, Inc) connected to a differential pressure transducer (TP-602T, ±5 cm H2O), and VT was calculated by digital integration. The heated humidifier was turned off during these protocols. After each experimental setting was changed, we allowed ≥5 min for stabilization. The FIO2 of inspired gas downstream of the external nares was measured for 1 min using an oxygen analyzer (LZ100), and data for the final 3 breaths were extracted. The oxygen analyzer was calibrated at FIO2 of 0.21 and 1.0. The pneumotachometer was calibrated with a supersyringe. All signals were processed through an analog/digital converter and saved on a computer at 50 Hz/channel using data acquisition software (WinDaq, Dataq Instruments, Akron, Ohio).
Statistics
At each experimental setting, we gathered FIO2 data for 3 breaths. Analysis of variance was performed using repeated measures, and results are expressed as mean ± SD. All statistical tests were 2-sided, and P < .01 was considered statistically significant. All statistical analysis was performed using commercial software (SPSS 11.01, SPSS, Chicago, Illinois).
Results
With the HFNC system, when FIO2 was set at 0.3, 0.5, and 0.7, oxygen concentration at the flow meter outlet was 0.31 ± 0.01, 0.51 ± 0.01, and 0.71 ± 0.01. With the conventional nasal cannula, when FIO2 was set at 1.0, oxygen concentration was 1.00 ± 0.001. With HFNC, when gas flow was set at 20, 40, and 60 L/min, measured flow was 20.5 ± 0.3, 40.6 ± 0.7, and 58.8 ± 0.2 L/min; with the conventional nasal cannula, when gas flow was set at 2, 4, and 6 L/min, measured flow was 2.1 ± 0.3, 4.1 ± 0.2, and 6.2 ± 0.1 L/min. At HFNC gas flow of 20, 40, and 60 L/min, end-expiratory pressure of the lung compartment was 1.3 ± 0.3, 1.8 ± 0.3, and 2.2 ± 0.3 cm H2O with the small prong; 1.7 ± 0.4, 2.8 ± 0.5, and 4.8 ± 0.5 cm H2O with the medium prong; and 2.3 ± 0.6, 5.3 ± 0.6, and 10.3 ± 1.3 cm H2O with the large prong.
As the set FIO2 increased, the difference between set and measured FIO2 increased (P < .001). The differences were 0.001 ± 0.017, 0.040 ± 0.048, and 0.073 ± 0.081 at set FIO2 of 0.3, 0.5, and 0.7.
Effect of VT and Gas Flow During HFNC
At HFNC, gas flows of 20 and 40 L/min, as VT increased, measured FIO2 decreased from set value (P < .001). At 60 L/min, whereas measured FIO2 was not affected by VT when FIO2 was set at 0.3 and 0.5, when FIO2 was set at 0.7, as VT increased, measured FIO2 decreased from set value (P = .001) (Table 1) (Fig. 2).
Effect of Tidal Volume and High-Flow Nasal Cannula Gas Flow on FIO2
Effect of changing VT and flow during high-flow nasal cannula (HFNC) with FIO2 of 0.3 (A), 0.5 (B), and 0.7 (C). With HFNC flows of 20 and 40 L/min, measured FIO2 was affected by VT at all FIO2 settings. With HFNC flow of 60 L/min, measured FIO2 was not affected by VT when FIO2 was set at 0.3 and 0.5; when FIO2 was set at 0.7, however, as VT increased, measured FIO2 decreased. *, P < .01.
Effect of VT and Gas Flow During Conventional Nasal Cannula Delivery
As VT increased, measured FIO2 statistically significantly decreased at all gas flows (P < .001) (Fig. 3). Measured FIO2 during low-flow delivery with VT of 300, 500, and 700 mL was 0.37 ± 0.01, 0.32 ± 0 and 0.29 ± 0 at 2 L/min; 0.45 ± 0.01, 0.39 ± 0.01, and 0.34 ± 0 at 4 L/min; and 0.58 ± 0.01, 0.45 ± 0.01, and 0.40 ± 0 at 6 L/min.
Effects of changing VT and flow during low-flow oxygen delivery As VT increased, measured FIO2 decreased significantly at all flow settings. *, P <.001.
Effect of Breathing Frequency
We found no effect of breathing frequency on measured FIO2. Measured FIO2 values at breathing frequencies of 10 and 20 breaths/min during HFNC were: at set FIO2 = 0.3, 0.29 ± 0.02 and 0.29 ± 0.02; at set FIO2 = 0.5, 0.46 ± 0.05 and 0.46 ± 0.05; and at set FIO2 = 0.7, 0.63 ± 0.08 and 0.63 ± 0.08. Measured FIO2 with the conventional nasal cannula at 10 and 20 breaths/min was 0.40 ± 0.08 and 0.40 ± 0.09.
Effect of Prong Size During HFNC
When we tested different prong sizes, we found no differences in measured FIO2.
Discussion
In this bench study, we evaluated how HFNC flow, VT, breathing frequencies, and prong sizes affected measured FIO2 during simulated spontaneous breathing. When HFNC gas flow was <40 L/min, measured FIO2 was affected by VT. As the FIO2 set value was increased, the difference between the set value and measured FIO2 increased. As HFNC gas flow increased, measured FIO2 increased more toward the set value.
As a working hypothesis, if we assume that when HFNC gas flow is set at 20, 40, and 60 L/min, if all of the HFNC gas flow is inhaled, then measured FIO2 would depend on the relationship between the VT of spontaneous breathing and HFNC gas flow. When inspiratory flow is less than HFNC gas flow, the patient would, in theory, inhale the gas delivered via HFNC, and measured FIO2 would consequently show good correspondence with set FIO2. If inspiratory flow were greater than HFNC flow, however, both delivered gas and ambient air would be inhaled. Chanques et al10 previously reported that actual FIO2 of the trachea in subjects with high-flow oxygen therapy increased as HFNC flow increased. When VT was set at 300, 500, and 700 mL and inspiratory time was set at 1 s with a decelerating flow waveform, spontaneous breathing inspiratory peak flow was 33, 55, and 77 L/min. At VT = 300 mL, for one third of the inspiratory time, spontaneous breathing inspiratory flow was >20 L/min. When VT was 500 mL, for one fourth of the inspiratory time, spontaneous breathing inspiratory flow was >40 L/min. Consequently, with HFNC gas flow of 20 and 40 L/min, measured FIO2 was affected by VT. The difference between set FIO2 and measured FIO2 (ΔFIO2) was more apparent when set FIO2 was high because the difference between the set FIO2 and the FIO2 of air (0.21) was greater. At VT = 700 mL, when HFNC gas flow was 20 L/min, ΔFIO2 was 0.04, 0.14, and 0.24 at set FIO2 of 0.3, 0.5, and 0.7, respectively; when HFNC gas flow was 40 L/min, ΔFIO2 was 0.01, 0.05, and 0.09 at set FIO2 of 0.3, 0.5, and 0.7, respectively.
With a conventional nasal cannula, changes in VT statistically significantly affected measured FIO2 at all flow levels: At 6 L/min and VT 300 mL, measured FIO2 was 0.58 ± 0.01, whereas it was 0.40 ± 0 with VT of 700 mL. There have been other reports that oxygen is delivered more efficiently by high-flow than by low-flow systems.12,13 Maggiore et al14 compared 2 high-flow systems on oxygenation for the same set FIO2 after extubation. Compared with the air-entrainment mask, HFNC resulted in better oxygenation, whereas it is unclear whether actual FIO2 was lower with the air-entrainment mask.
Breathing frequency and prong size did not affect measured FIO2. Similarly, in a previous bench study by Chikata et al15 on the effect of breathing frequencies and prong size on humidification during HFNC, neither breathing frequency nor prong size influenced humidification during HFNC.
This study has some limitations. Derived from a bench study, the results cannot be directly applied to clinical settings. It only simulated closing of the mouth. Inspiratory time and inspiratory flow were fixed regardless of breathing frequency. In real life, as breathing frequency increases, inspiratory flow increases and inspiratory time decreases.
The present study was, moreover, carried out using only one inspiratory flow waveform, and the nasal prongs were firmly fixed into the modeled external nares. In real life, peak inspiratory flow varies breath-by-breath in each patient, and the position of the prongs frequently varies.
Conclusions
In a bench study, during HFNC, we investigated measured FIO2 under various spontaneous breathing conditions and with different prong sizes. When HFNC gas flow was less than 40 L/min, measured FIO2 was affected by high VT. HFNC gas delivery, however, was much less affected by changes in VT than was conventional nasal cannula delivery.
Footnotes
- Correspondence: Masaji Nishimura MD PhD, Critical Care and Emergency Medicine, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan. Tel.: 81-88-633-9445; Fax: 81-88-633-9425; E-mail: nmasaji{at}tokushima-u.ac.jp.
The authors have disclosed no conflicts of interest.
- Copyright © 2017 by Daedalus Enterprises
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