Oxygen delivery through high-flow nasal cannulae increase end-expiratory lung volume and reduce respiratory rate in post-cardiac surgical patients

Progressive dyspnea and exercise intolerance are common reasons why patients with severe chronic obstructive pulmonary disease (COPD) seek medical help.1 Patients with COPD have expiratory flow limitation that causes air trapping.2 Respiratory infections or environmental factors (seasonal change, poor air quality, etc.) can lead to increases in airway resistance and mucous production and complicate expiratory flow limitation, thus leading to worsened air trapping. Hyperinflation from air trapping has multiple negative physiologic consequences such as increased dyspnea, decreased exercise tolerance and worsened quality of life.3 Therapies that can reduce hyperinflation may improve respiratory symptoms as well as outcomes in patients with COPD. High flow nasal cannula (HFNC) has been shown to be an effective modality in treating critically ill patients with acute hypoxemic respiratory failure.4 Multiple reasons have been suggested to account for the benefits associated with HFNC and include improved oxygenation, reduced work of breathing, an increase in end expiratory lung volume, washout of nasopharyngeal dead space, altered breathing pattern and improved mucociliary clearance.5-7 Most of these mechanistic studies have been conducted using bench or animal models or healthy volunteers.8 Data regarding its use in patients with COPD, however, are limited and the mechanisms of potential benefit in this patient population are uncertain. In this issue, Atwood and colleagues provide important insight into the possible benefits associated with HFNC in patients with moderate to severe, stable COPD.9 They sequentially studied 32 patients with stable COPD treated with 1-2 L minute home oxygen, on no therapy and then subsequently randomly assigned them to HFNC and their prescribed level of low flow oxygen. HFNC reduced respiratory rates compared to the no therapy and low flow oxygen conditions without any increase in tidal volume or change in levels of arterial carbon dioxide. Oxygenation with HFNC was lower when compared to low flow oxygen but similar to the control. The reduction in ventilatory effort with HFNC with no change in carbon dioxide or oxygenation parameters suggests that HFNC purges the anatomic dead space of carbon dioxide and thereby improves ventilatory efficiency. These data support prior studies showing that HFNC reduces respiratory rate in COPD patients during hospitalization or performing exercise. However, these studies were limited because supplemental oxygen was also administered to treat concurrent moderate to severe hypoxemia.10,11 In this study, the use of HFNC independent of oxygen administration in stable COPD provides important information that washout of nasopharyngeal dead space results in a reduction in respiratory rate and stable oxygenation and carbon dioxide levels thus indicating an improved respiratory efficiency. Limitations of the study includes its short-term assessment period, lack of assessment of the add on effects of supplemental oxygen on gas exchange changes and no information on the benefits, if any, of enhanced humidification. Its strengths are that the population represented stable COPD and the opportunity to assess patients without supplemental oxygenation allowed the investigators to detail the impact of purging the conducting airway of carbon dioxide on improving ventilatory efficiency. HFNC may have important benefits for patients with COPD by improving gas exchange, decreasing breathlessness and improving exercise tolerance. To understand the clinical benefits that can be achieved due to these mechanistic effects, additional studies that explore the impact of long term use of HFNC on important clinical parameters such as exacerbation frequency, hospitalization, sleep quality and quality of life are needed.

High-flow nasal cannula (HFNC) enables delivery of humidified gas at high flow while controlling the FIO2 . Although its use is growing in patients with acute respiratory failure, little is known about the impact of HFNC on lung volume. Therefore, we aimed to assess lung volume changes in healthy subjects at different flows and positions. This was a prospective physiological study performed in 16 healthy subjects. The changes in lung volumes were assessed by measuring end-expiratory lung impedance by using electrical impedance tomography. All the subjects successively breathed during 5 min in these following conditions: while in a supine position without HFNC (T0) and 3 measurements in a semi-seated position at 45° without HFNC (T1), and with HFNC at a flow of 30 L/min (T2), and 50 L/min (T3). Compared with the supine position, the values of end-expiratory lung impedance significantly increased with the subjects in a semi-seated position. End-expiratory lung impedance significantly increased after HFNC initiation in subjects in a semi-seated position and further increased by increasing flow at 50 L/min. When taking the end-expiratory lung impedance measurement in subjects in a semi-seated position (T1) as reference, the differences among the medians of global end-expiratory lung impedance were statistically significant (P < .001), which amounted to 1.05 units in T1; 1.12 units in T2; and 1.44 units in T3 (P < .05 for all comparisons, Wilcoxon test). The breathing frequency did not differ between the supine and semi-seated position (T0 and T1) but significantly decreased after initiation of HFNC and further decreased at high flow. T0 and T1 were not different (P = .13); whereas there was a statistically significant difference among T1, T2, and T3 (P < .05, post hoc test with Bonferroni correction). In healthy subjects, the semi-seated position and the use of HFNC increased end-expiratory lung impedance globally. These changes were accompanied by a significant decrease in the breathing frequency.

PurposeTo study and compare the relationship between end-expiratory lung volume (EELV) and changes in end-expiratory lung impedance (EELI) measured with electrical impedance tomography (EIT) at the basal part of the lung at different PEEP levels in a mixed ICU population.MethodsEnd-expiratory lung volume, EELI and tidal impedance variation were determined at four PEEP levels (15–10–5–0 cm H2O) in 25 ventilated ICU patients. The tidal impedance variation and tidal volume at 5 cm H2O PEEP were used to calculate change in impedance per ml; this ratio was then used to calculate change in lung volume from change in EELI. To evaluate repeatability, EELV was measured in quadruplicate in five additional patients.ResultsThere was a significant but relatively low correlation (r = 0.79; R2 = 0.62) and moderate agreement (bias 194 ml, SD 323 ml) between ∆EELV and change in lung volume calculated from the ∆EELI. The ratio of tidal impedance variation and tidal volume differed between patients and also varied at different PEEP levels. Good agreement was found between repeated EELV measurements and washin/washout of a simulated nitrogen washout technique.ConclusionDuring a PEEP trial, the assumption of a linear relationship between change in global tidal impedance and tidal volume cannot be used to calculate EELV when impedance is measured at only one thoracic level just above the diaphragm.Electronic supplementary materialThe online version of this article (doi:10.1007/s00134-009-1512-6) contains supplementary material, which is available to authorized users.

A bedside tool for monitoring changes in end-expiratory lung volume (ΔEELV) would be helpful to set optimal positive end-expiratory pressure (PEEP) in acute lung injury/acute respiratory distress syndrome patients. The hypothesis of this study was that the cumulative difference of the inspiratory and expiratory tidal volumes of the first 10 breaths after a PEEP change accurately reflects the change in lung volume following a PEEP alteration. Changing PEEP induces lung volume changes, which are reflected in differences between inspiratory and expiratory tidal volumes measured by spirometry. By adding these differences with correction for offset, for the first 10 breaths after PEEP change, cumulative tidal volume difference was calculated to estimate ΔEELV(VT) ((i-e)) . This method was evaluated in a lung model and in patients with acute respiratory failure during a PEEP trial. In patients, ΔEELV(VT) ((i-e)) were compared with simultaneously measured changes in lung impedance, by electric impedance tomography (EIT), using calibration vs. tidal volume to estimate changes in ΔEELV(EIT) . In the lung model, there was close correlation (R(2) = 0.99) between ΔEELV(VT) ((i-e)) and known lung model volume difference, with a bias of -4 ml and limits of agreement of 42 and -50 ml. In 12 patients, ΔEELV(EIT) was closely correlated to ΔEELV(VT) ((i-e)) (R(2) = 0.92), with mean bias of 50 ml and limits of agreement of 131 and -31 ml. Changes in EELV estimated by EIT (ΔEELV(EIT) ) exceeded measurements by spirometry (ΔEELV(VT) ((i-e)) ), with 15 (±15)%. We conclude that spirometric measurements of inspiratory-expiratory tidal volumes agree well with impedance changes monitored by EIT and can be used bedside to estimate PEEP-induced changes in EELV.

High-flow nasal cannula (HFNC) therapy improves oxygenation and increases end-expiratory lung volume (EELV). Asymmetric cannulas are a novel interface, but their interaction with body position and breathing route (mouth open vs closed) on EELV is unclear. This study used electrical impedance tomography (EIT) to assess the impact of these factors on end-expiratory lung impedance (EELI), a surrogate for EELV, in healthy subjects. This prospective, randomized crossover physiological study included 16 healthy volunteers who received HFNC via an asymmetric cannula. EELI was measured across different body positions (Semi-Fowler's, High Fowler's, flat [180°] prone, and reverse Trendelenburg, flows (40 and 60 L/min), and mouth conditions (open/closed). A linear mixed-effects model compared EELI changes from baseline. The greatest significant increase in global EELI occurred in the reverse Trendelenburg at 60 L/min with the mouth closed (difference = 2.07, P < .001). This condition was significantly superior to most other combinations. Mouth closure was a critical factor for increasing EELI. The reverse Trendelenburg specifically enhanced EELI in dorsal lung regions at high flow with a closed mouth. Body position, flow setting, and mouth condition significantly impactedEELV during asymmetric HFNC. The combination of the reverse Trendelenburg, high flow (60 L/min), and mouth closure resulted in the greatest increase in EELV and promoted more homogeneous lung ventilation in healthy subjects. Encouraging nasal breathing and optimizing positioning could enhance the physiological benefits of HFNC.

BackgroundLarge tidal volumes during de novo acute hypoxemic respiratory failure (AHRF) may promote patient self-inflicted lung injury. Tidal volume assessment under high flow nasal cannula (HFNC) is not routinely feasible at the bedside. Our objective was to determine whether tidal volume during low-level continuous positive airway pressure (CPAP) could predict tidal volume during HFNC and to compare the physiological effects of HFNC and low-level CPAP.MethodsProspective, single-center study including 29 de novo AHRF patients treated with HFNC (50 to 60 L.min− 1). Patients were monitored using electrical impedance tomography during HFNC then CPAP at 4 cmH2O. Tidal volume during HFNC was calculated based on tidal impedance variation. The ability of tidal volume under low-level CPAP to predict tidal volume under HFNC was explored using Bland-Altman analysis. CPAP and HFNC were compared in terms of tidal volume, minute ventilation, respiratory comfort, dyspnea, oxygenation, ventilation distribution, end-expiratory lung volume, thoraco-abdominal asynchrony and recruitment.ResultsUnder HFNC, patients had a tidal volume of 6.6 (5.9–8.7) mL.kg− 1 PBW. 20 (69%) patients exhibited a tidal volume between 4 and 8 mL.kg− 1 PBW, while in 5 (17%) patients it exceeded 9 mL.kg− 1 PBW. Tidal volume under CPAP was higher (9.4 (8.3–11) mL.kg− 1 PBW, p < 0.001). Tidal volumes under CPAP and under HFNC were modestly correlated (Spearman r = 0.50, p = 0.005). Bland-Altman analysis showed a bias of 2.4 mL.kg− 1, with limits of agreement ranging from − 1.1 mL.kg− 1to 5.9 mL.kg− 1. Nevertheless, a larger (> 11.5 mL.kg− 1 PBW ) tidal volume under low-level CPAP predicted a larger (> 9 mL.kg− 1 PBW ) tidal volume under HFNC with 80% sensitivity and 96% specificity. Low-level CPAP was associated with increased minute ventilation, end-expiratory lung volume, and oxygenation as compared to HFNC. It decreased signs of respiratory distress in the most severe patients but was associated with lower comfort compared to HFNC.ConclusionAmong ICU patients with de novo AHRF, tidal volume under HFNC was mostly protective. Tidal volume during CPAP at 4 cmH2O did not predict tidal volume during HFNC. Such low-level CPAP was associated with increased tidal volume, minute ventilation, end-expiratory volume, and oxygenation.Trial registrationClinicalTrials.gov ID NCT03919331. Registration date: 2019-03-26.

Paradoxical Effect of Chest Wall Compression on Respiratory System Compliance: A Multicenter Case Series of Patients With ARDS, With Multimodal Assessment

Electrical impedance tomography (EIT) is a noninvasive imaging modality that allows real-time monitoring of regional lung ventilation. The aim of the study is to investigate whether fast saline infusion causes changes in lung impedance that could affect the interpretation of EIT data. Eleven pigs were anaesthetized and mechanically ventilated. A bolus of 500 mL of normal saline was administered rapidly. Two PEEP steps were performed to allow quantification of the effect of normal saline on lung impedance. The mean change of end-expiratory lung impedance (EELI) caused by the saline bolus was equivalent to a virtual decrease of end-expiratory lung volume (EELV) by 227 (188–250) mL and decremental PEEP step of 4.40 (3.95–4.59) cmH2O (median and interquartile range). In contrast to the changes of PEEP, the administration of normal saline did not cause any significant differences in measured EELV, regional distribution of lung ventilation determined by EIT or in extravascular lung water and intrathoracic blood volume. In conclusion, EELI can be affected by the changes of EELV as well as by the administration of normal saline. These two phenomena can be distinguished by analysis of regional distribution of lung ventilation.

Biomedical research is becoming more complex as a result of involvement by individual investigators, universities, commercial research units, and industry.Financial conflicts of interest have been the subject of many editorials, and most peer-

High-flow nasal cannula (HFNC) improves the clinical outcomes of nonintubated patients with acute hypoxemic respiratory failure (AHRF). To assess the effects of HFNC on gas exchange, inspiratory effort, minute ventilation, end-expiratory lung volume, dynamic compliance, and ventilation homogeneity in patients with AHRF. This was a prospective randomized crossover study in nonintubated patients with AHRF with PaO2/setFiO2 less than or equal to 300 mm Hg admitted to the intensive care unit. We randomly applied HFNC set at 40 L/min compared with a standard nonocclusive facial mask at the same clinically set FiO2 (20 min/step). Toward the end of each phase, we measured arterial blood gases, inspiratory effort, and work of breathing by esophageal pressure swings (ΔPes) and pressure time product, and we estimated changes in lung volumes and ventilation homogeneity by electrical impedance tomography. We enrolled 15 patients aged 60 ± 14 years old with PaO2/setFiO2 130 ± 35 mm Hg. Seven (47%) had bilateral lung infiltrates. Compared with the facial mask, HFNC significantly improved oxygenation (P < 0.001) and lowered respiratory rate (P < 0.01), ΔPes (P < 0.01), and pressure time product (P < 0.001). During HFNC, minute ventilation was reduced (P < 0.001) at constant arterial CO2 tension and pH (P = 0.27 and P = 0.23, respectively); end-expiratory lung volume increased (P < 0.001), and tidal volume did not change (P = 0.44); the ratio of tidal volume to ΔPes (an estimate of dynamic lung compliance) increased (P < 0.05); finally, ventilation distribution was more homogeneous (P < 0.01). In patients with AHRF, HFNC exerts multiple physiologic effects including less inspiratory effort and improved lung volume and compliance. These benefits might underlie the clinical efficacy of HFNC.

BackgroundThe incidence of obesity is increasing worldwide. In selected individuals, bariatric surgery may offer a means of achieving long-term weight loss, improved health, and healthcare cost reduction. Physiological changes that occur because of obesity and general anaesthesia predispose to respiratory complications following bariatric surgery. The aim of this study is to determine whether post-operative high flow nasal oxygen therapy (HFNO2) improves respiratory function and reduces the incidence of post-operative pulmonary complications (PPCs) in comparison to conventional oxygen therapy in these patients.MethodThe OXYBAR study is a prospective, un-blinded, single centre, randomised, controlled pilot study. Patients with body mass index (BMI) > 30 kg/m2, undergoing laparoscopic bariatric surgery, will be randomised to receive either standard low flow oxygen therapy or HFNO2 in the post-operative period. The primary outcome measure is the change in end expiratory lung impedance (∆EELI) as measured by electrical impedance tomography (EIT). Secondary outcome measures include change in tidal volume (∆Vt), partial arterial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, incidence of PPCs, hospital length of stay and measures of patient comfort.DiscussionWe hypothesise that the post-operative administration of HFNO2 will increase EELI and therefore end expiratory lung volume (EELV) in obese patients. To our knowledge this is the first trial designed to assess the effects of HFNO2 on EELV in this population. We anticipate that data collected during this pilot study will inform a larger multicentre trial.Trial registrationAustralian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000694314. Registered on 15 May 2017.

The aim of this prospective randomized crossover study was to compare the short-term effects of high-flow nasal cannula (HFNC) therapy and a 45° head-up tilt to the short-term effects of conventional oxygen (O2) therapy in post-abdominal surgery patients. A total of 18 subjects who were successfully weaned from ventilator support after abdominal surgery were included in the study. The subjects were randomly assigned to 2 groups: conventional O2 was applied in group A for 15 min, and HFNC (60 L/min) was applied in group B for 15 min. A 15-min washout period with conventional O2 was performed before the interventions were switched in both groups. Heart rate, blood pressure, breathing frequency, ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen (PaO2 /FIO2 ), and subject-reported comfort scores were recorded. Changes in end-expiratory lung impedance (EELI) were calculated with electrical impedance tomography. Results are presented as the percent change in lung volume compared to baseline during volume-controlled continuous mandatory ventilation before extubation. HFNC improved EELI in both the ventral (conventional O2 vs HFNC, -48.2% ± 41.0 vs -30.0% ± 40.3, P < .001) and the dorsal (conventional O2 vs HFNC, -37.0% ± 75.9 vs -26.5% ± 68.4, P = .02) regions of the lungs. Subjective subject-reported scores indicated that HFNC was more comfortable than conventional O2 (conventional O2 vs HFNC, 5.8 ± 1.5 vs 6.9 ± 1.9, P = .02). No differences were found in the other examined parameters. A head-up tilt position with conventional O2 improved EELI in the dorsal regions (55.9% ± 100.1, P < .001) but not in the ventral regions (-37.9% ± 43.1%, P = .38) of the lungs compared to HFNC or conventional O2 alone. In post-abdominal surgery subjects who had been extubated, HFNC improved lung volume and patient comfort. A head-up tilt position introduced a heterogeneous increase in EELI in the dorsal regions of the lungs. HFNC therapy may be beneficial in this patient group. (ChiCTR1900020886, http://chictr.org.cn).

Electrical impedance tomography measures changes in lung impedance, which are mainly related to changes in lung volume. We used electrical impedance tomography to investigate the effects of high-flow nasal cannula (HFNC) and body position on global and regional end-expiratory lung impedance variation (ΔEELI). Prospective study with 20 healthy adults. Two periods were defined: the first in supine position and the second in prone position. Each period was divided into 3 phases. In the first and the third phases the subjects were breathing ambient air, and in the second HFNC was implemented. Four regions of interest were defined: 2 ventral and 2 dorsal. For each respiratory cycle, global and regional ΔEELI were measured by electrical impedance tomography and were expressed as a function of the tidal variation of the first stable respiratory cycle (units). HFNC increased global EELI by 1.26 units (95% CI 1.20-1.31, P < .001) in supine position, and by 0.87 units (95% CI 0.82-0.91, P < .001) in prone position. The distribution of ΔEELI was homogeneous in prone position, with no difference between ventral and dorsal lung regions (-0.01 units, 95% CI -0.01 to 0, P = .18), while in supine position a significant difference was found (0.22 units, 95% CI 0.21-0.23, P < .001) with increased EELI in ventral areas. HFNC increased global EELI in our population, regardless of body position, suggesting an increase in functional residual capacity. Prone positioning was related to a more homogeneous distribution of ΔEELI, while in supine position ΔEELI was higher in the ventral lung regions.

Rationale: The respective effects of positive end-expiratory pressure (PEEP) and pressure support delivered through the helmet interface in patients with hypoxemia need to be better understood. Objectives: To assess the respective effects of helmet pressure support (noninvasive ventilation [NIV]) and continuous positive airway pressure (CPAP) compared with high-flow nasal oxygen (HFNO) on effort to breathe, lung inflation, and gas exchange in patients with hypoxemia (PaO2/FiO2 ⩽ 200). Methods: Fifteen patients underwent 1-hour phases (constant FiO2) of HFNO (60 L/min), helmet NIV (PEEP = 14 cm H2O, pressure support = 12 cm H2O), and CPAP (PEEP = 14 cm H2O) in randomized sequence. Measurements and Main Results: Inspiratory esophageal (ΔPES) and transpulmonary pressure (ΔPL) swings were used as surrogates for inspiratory effort and lung distension, respectively. Tidal Volume (Vt) and end-expiratory lung volume were assessed with electrical impedance tomography. ΔPES was lower during NIV versus CPAP and HFNO (median [interquartile range], 5 [3-9] cm H2O vs. 13 [10-19] cm H2O vs. 10 [8-13] cm H2O; P = 0.001 and P = 0.01). ΔPL was not statistically different between treatments. PaO2/FiO2 ratio was significantly higher during NIV and CPAP versus HFNO (166 [136-215] and 175 [158-281] vs. 120 [107-149]; P = 0.002 and P = 0.001). NIV and CPAP similarly increased Vt versus HFNO (mean change, 70% [95% confidence interval (CI), 17-122%], P = 0.02; 93% [95% CI, 30-155%], P = 0.002) and end-expiratory lung volume (mean change, 198% [95% CI, 67-330%], P = 0.001; 263% [95% CI, 121-407%], P = 0.001), mostly due to increased aeration/ventilation in dorsal lung regions. During HFNO, 14 of 15 patients had pendelluft involving >10% of Vt; pendelluft was mitigated by CPAP and further by NIV. Conclusions: Compared with HFNO, helmet NIV, but not CPAP, reduced ΔPES. CPAP and NIV similarly increased oxygenation, end-expiratory lung volume, and Vt, without affecting ΔPL. NIV, and to a lesser extent CPAP, mitigated pendelluft. Clinical trial registered with clinicaltrials.gov (NCT04241861).

SUCCESSFUL USE OF HIGH FLOW NASAL CANNULA OUTSIDE OF THE CRITICAL CARE AREAS