Conservative versus liberal oxygen therapy for intensive care unit patients: meta-analysis of randomized controlled trials.

BACKGROUND: It remains unclear whether conservative oxygen therapy (COT) or liberal oxygen therapy (LOT) is more beneficial to the clinical outcomes of intensive care unit (ICU) patients. We systematically reviewed the efficacy and safety of conservative versus liberal oxygen therapy for ICU patients. METHODS: We systematically searched PubMed, Embase, Web of Science, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, MedRxiv, and BioRxiv for reports on randomized controlled trials (RCTs) that compared the effects of COT versus LOT on the clinical outcomes of ICU patients published in English before April 2024. The primary outcome was the mortality rate, secondary outcomes included ICU and hospital length of stay, days free from mechanical ventilation support (MVF), vasopressor-free time (VFT), and adverse events. RESULTS: In all, 13 RCTs involving 10,632 patients were included in analyses. Meta-analysis showed COT did not reduce mortality at 30-day (risk ratio [RR] = 1.01, 95% confidence interval [CI] 0.94 to 1.09, I2 = 42%, P = 0.78), 90-day (RR = 1.01, 95% CI 0.95 to 1.08, I2 = 9%, P = 0.69), or longest follow-up (RR = 1.00, 95% CI 0.95 to 1.06, I2 = 22%, P = 0.95) compared to LOT in ICU patients. In subgroup analyses, no significant difference was observed between the two groups in terms of the different ICU, baseline P/F, and actual PaO2. In addition, COT did not affect ICU length of stay, hospital length of stay, or VFT, it only affected MVF days. CONCLUSIONS: COT did not reduce all-cause mortality in ICU patients. Further RCTs are urgently needed to confirm the impact of COT strategy on specific populations.

Comparison between high-flow nasal cannula and conventional oxygen therapy in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) are important respiratory support strategies for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the results are conflicting for the risk of intubation with HFNC as compared to COT. OBJECTIVES: We systematically synthesized the outcomes of HFNC relative to COT in COVID-19 patients with AHRF and evaluated these outcomes in relevant subpopulations. DESIGN: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES AND METHODS: We searched PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, medRxiv, BioRxiv, and the Cochrane Central Register of Controlled Trials for randomized controlled trials and observational studies that compared the efficacy of HFNC with COT in patients with COVID-19-related AHRF. Primary outcomes were intubation rate and mortality rate. Secondary outcomes were the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2), respiratory rate, hospital length of stay, intensive care unit (ICU) length of stay, and days free from invasive mechanical ventilation. RESULTS: In total, 20 studies with 5732 patients were included. We found a decreased risk of requiring intubation in HFNC compared to COT [odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.46-0.82, p = 0.0009, I2 = 75%]. Similarly, we found HFNC was associated with lower risk of intubation rate compared to COT in the subgroup of patients with baseline PaO2/FiO2 < 200 mmHg (OR = 0.69, 95% CI: 0.55-0.86, p = 0.0007, I2 = 45%), and who were in ICU settings at enrollment (OR = 0.57, 95% CI: 0.38-0.85, p = 0.005, I2 = 80%). HFNC was associated with an improvement of PaO2/FiO2 and respiratory rate compared to COT. The use of HFNC compared to COT did not reduce the mortality rate, days free from invasive mechanical ventilation, hospital length of stay, or ICU length of stay. CONCLUSION: Compared to COT, HFNC may decrease the need for tracheal intubation in patients with COVID-19-related AHRF, particularly among patients with baseline PaO2/FiO2 < 200 mmHg and those in ICU settings. TRIAL REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022339072).

Effects of jet nebulization on ventilator performance with different invasive ventilation modes: A bench study.

Background: The effects of jet nebulization on ventilator performance in the volume control mode (VC) and pressure control mode (PC) of ventilation have not been determined. Objectives: The present study investigated the impact of jet nebulization on ventilator performance in different modes in vitro. Methods: Two types of jet nebulizer (ventilator-integrated jet nebulizers, external jet nebulizer) and six types of ventilator were connected with a simulated lung to simulate aerosol therapy during mechanical ventilation. The ventilation modes were set to VC and PC, and the driving flows of external jet nebulizer were set at 4 L/min and 8 L/min, respectively. Jet nebulizers were placed between patient airway and Y-piece or at 15 cm from the Y-piece in the inspiratory limb. The effects of jet nebulization were compared with the baseline of triggering performance, control performance, and tidal volume under different experimental conditions. Results: Ventilator-integrated jet nebulizers had no effect on ventilator performance in different modes (all P > 0.05). However, the effects of external jet nebulizers on ventilator performance varied widely: for triggering performance, all parameters were increased in different modes and nebulization positions (all P < 0.05), including the time from the beginning of the inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator (TPmin), the time to trigger (Ttrig), and the magnitude of airway pressure drop needed to trigger (Ptrig); for control performance, peak inspiratory pressure (Ppeak) and peak inspiratory flow(Pflow) were increased in the VC mode (P < 0.05), but not significantly changed in the PC mode (P > 0.05);the actual tidal volume (VT) and expiratory tidal volume monitored (VTe) were significantly increased (P < 0.05), however, the inspiratory tidal volume monitored (VTi) was not affected by jet nebulization in the VC mode. In the PC mode, there were no significant changes in VT, whereas VTi decreased and VTe increased (P < 0.05). The higher the driving flow of external jet nebulizers, the stronger the impact on ventilator performance (all P < 0.05). Conclusion: Triggering performance was decreased in both the VC and PC modes when using an external jet nebulizer, while the effects of nebulization on control performance and tidal volume varied significantly.

Position of different nebulizer types for aerosol delivery in an adult model of mechanical ventilation.

Background: The optimal positions of different types of nebulizer for aerosol delivery remain unclear. Methods: Three ICU ventilators employing three types of nebulizer were separately connected to a simulated lung to simulate nebulization during invasive ventilation. Assist/control-pressure control (A/C-PC) mode was utilized, with inspiratory pressure (Pi) set to 12 cmH2O and positive end expiratory pressure (PEEP) set to 5 cmH2O, and with a target Vt of 500 ml. The bias flow of all the ventilators was set to 2 L/min. The three nebulizers were the continuous jet nebulizer (c-JN), the inspiratory synchronized jet nebulizer (i-JN), and the vibrating mesh nebulizer (VMN). The five nebulizer positions were as follows: at the Y-piece (position 1) and 15 cm from the Y-piece (position 2) between the endotracheal tube and the Y-piece, at the Y-piece (position 3) and 15 cm from the Y-piece (position 4) in the inspiratory limb; and at the humidifier inlet (position 5). Aerosols were collected with a disposable filter placed at the simulated lung outlet (n = 3) and were measured by UV spectrophotometry (276 nm). The measurements were compared under different experimental conditions. Results: The aerosol delivery of c-JN, i-JN, and VMN was 5.33 ± 0.49~11.12 ± 0.36%, 7.73 ± 0.76~13.75 ± 0.46% and 11.13 ± 56-30.2 ± 1.63%, respectively. The higher aerosol delivery: for c-JN~Positions 2 (10.95 ± 0.15%), fori-JN~Positions 1 or 2 (12.91 ± 0.88% or 13.45 ± 0.42%), for VMN~Positions 4(29.03 ± 1.08%); the lower aerosol delivery: for c-JN~Positions 1, 3 or 5, fori-JN~Positions 4 or 5, for VMN~Positions 5.The highest aerosol delivery:For c-JN at Position 2 (10.95 ± .15%), for i-JN at Position 1 or 2 (12.91 ± .88% or 13.45 ± .42%), for VMN at Positions 4 (29. 03 ± 1.08%); the lower aerosol delivery: for c-JN at Positions 1, 3 or 5, for i-JN at Positions 4 or 5, for VMN at Positions 5. The highest aerosol deliveryof c-JN was lower than that of i-JN while the VMN was the highest (all P < .05). However, no differences were observed between the highest aerosol delivery with c-JN and the lowest aerosol delivery with i-JN. Similar results were found between the lowest aerosol delivery with VMN and the highest aerosol delivery with c-JN /i-JN in the Avea ventilator. There were no differences in the highest aerosol delivery of each nebulizer among the different ventilators (all p > 0.05). Conclusion: During adult mechanical ventilation, the type and position of nebulizer influences aerosol delivery efficiency, with no differences between ventilators.

Comparison between high-flow nasal cannula and noninvasive ventilation in COVID-19 patients: a systematic review and meta-analysis.

BACKGROUND: High-flow nasal cannula (HFNC) and noninvasive ventilation (NIV) are important treatment approaches for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the differential impact of HFNC versus NIV on clinical outcomes of COVID-19 is uncertain. OBJECTIVES: We assessed the effects of HFNC versus NIV (interface or mode) on clinical outcomes of COVID-19. METHODS: We searched PubMed, EMBASE, Web of Science, Scopus, MedRxiv, and BioRxiv for randomized controlled trials (RCTs) and observational studies (with a control group) of HFNC and NIV in patients with COVID-19-related AHRF published in English before February 2022. The primary outcome of interest was the mortality rate, and the secondary outcomes were intubation rate, PaO2/FiO2, intensive care unit (ICU) length of stay (LOS), hospital LOS, and days free from invasive mechanical ventilation [ventilator-free day (VFD)]. RESULTS: In all, 23 studies fulfilled the selection criteria, and 5354 patients were included. The mortality rate was higher in the NIV group than the HFNC group [odds ratio (OR) = 0.66, 95% confidence interval (CI): 0.51-0.84, p = 0.0008, I2 = 60%]; however, in this subgroup, no significant difference in mortality was observed in the NIV-helmet group (OR = 1.21, 95% CI: 0.63-2.32, p = 0.57, I2 = 0%) or NIV-continuous positive airway pressure (CPAP) group (OR = 0.77, 95% CI: 0.51-1.17, p = 0.23, I2 = 65%) relative to the HFNC group. There were no differences in intubation rate, PaO2/FiO2, ICU LOS, hospital LOS, or days free from invasive mechanical ventilation (VFD) between the HFNC and NIV groups. CONCLUSION: Although mortality was lower with HFNC than NIV, there was no difference in mortality between HFNC and NIV on a subgroup of helmet or CPAP group. Future large sample RCTs are necessary to prove our findings. REGISTRATION: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022321997).

MDIG, a 2­oxoglutarate­dependent oxygenase, acts as an oncogene and predicts the prognosis of multiple types of cancer.

Recent studies have indicated that mineral dust­induced gene (MDIG) is an oncogene induced by environmental factors, which has a key role in the development and progression of various tumor types, through epigenetic modifications; however, there are no previous pan­cancer analyses of MDIG. In the present study, a comprehensive pan­cancer analysis of MDIG was performed using public databases. The results demonstrated that MDIG was upregulated in tumor tissue samples compared with normal tissue, that it was present in all cancer cell lines and it was closely associated with the prognosis of patients with different tumor types. Furthermore, MDIG expression was closely associated with the immunological characteristics of the tumor microenvironment (TME), such as the frequency of tumor­infiltrating immune cells, TME­relevant signatures, immunostimulatory genes, immune checkpoint genes, chemokine receptor genes, tumor mutational burden and microsatellite instability. In parallel, high expression of MDIG was associated with improved overall survival of patients and this was verified in a cohort of patients who had received anti­programmed cell death 1 ligand 1 treatment. Furthermore, high expression of MDIG led to multiple drug resistance in The Cancer Genome Atlas­lung adenocarcinoma cohort. In addition, gene set variant analysis and gene set enrichment analysis indicated that MDIG was involved in cell cycle regulation. In vitro experiments suggested that MDIG promoted cell proliferation through the mTOR complex 2/Akt and pyruvate dehydrogenase kinase 1/Akt signaling pathways. In summary, the present study suggests that MDIG may be a prognostic biomarker and therapeutic target for various cancer types.

Effect of Mask Selection on the Leak Test in Ventilators Designed for Noninvasive Ventilation.

BACKGROUND: The mask leak test used for modern noninvasive ventilators can detect the leak characteristics of masks that are not recommended by the manufacturer, but it has not yet been determined whether this method is acceptable. METHODS: A noninvasive ventilator equipped with a single-limb circuit and an oronasal mask was connected to a lung simulator. The ventilator was set to S/T mode, and inspiratory positive airway pressure/expiratory positive airway pressure was set to 10/5, 15/5, and 20/5 cm H2O, respectively. Eight nonmanufacturer-recommended oronasal masks were connected to the ventilator. The lung simulator was used to simulate COPD, restrictive disease, and normal lung, respectively. When switching between masks, the mask leak test was set to "Cancel" or "Start Test" in the noninvasive ventilator. The parameters displayed on the lung simulator and ventilator were recorded before and after the mask leak test. RESULTS: There were no significant difference before versus after the mask leak test for any lung simulator parameter, including trigger performance (ie, time from the beginning of the simulated inspiratory effort to the lowest value of airway pressure needed to trigger the ventilator, the magnitude of airway pressure drop needed to trigger, and time to trigger), inspiratory pressure delivery, PEEP, tidal volume, and displayed peak inspiratory pressure (all differences < 10%). At different noninvasive ventilation settings, tidal volumes displayed on the ventilator of the 3 masks were significantly different before and after mask leak test (all P < .05, and difference rate > 10%). CONCLUSIONS: The mask leak test had no effect on the ventilator performance when masks not recommended by the manufacturer were used, but tidal volume monitoring may be more accurate when some masks were used.

Adult with mass burnt lime aspiration: A case report and literature review.

BACKGROUND: Foreign body aspiration mainly occurs in children, which can cause a severe concurrent syndrome and even death without timely treatment. As a rare foreign body, aspiration of lime is seldom reported, and most cases involve a small amount of hydrated lime. Although the symptoms are usually severe, the prognosis is good after suitable treatment. Experience of treatment for lime aspiration is lacking, and this report provides novel evidence for treatment of mass burnt lime aspiration using bronchoscopy. CASE SUMMARY: We report an adult with a large amount of burnt lime aspiration. Because of delay in clearance of the inhaled lime in the trachea and bronchus at the local hospital, he suffered several severe complications, including complete occlusion of the right primary bronchus, aeropleura, aerodermectasia, pneumomediastinum, secondary infection and hypoxemia at 4 d after injury. After transferring to our department, bronchoscopy was immediately carried out to clear the lime in the major airway, using foreign body forceps, biopsy forceps, puncture needle, and hairbrush. The patient's condition recovered rapidly and at 3-months' follow-up, he demonstrated good recovery of the bronchus and lung parenchyma. CONCLUSION: After mass lime aspiration, flexible fiberoptic bronchoscopy is suggested as early as possible, using clamping, flushing or cryotherapy.

The Effect of Different Interfaces on the Aerosol Delivery with Vibrating Mesh Nebulizer During Noninvasive Positive Pressure Ventilation.

Background: The effect of different interfaces on the aerosol delivery with vibrating mesh nebulizer during noninvasive positive pressure ventilation (NIV) is not clear. Materials and Methods: Noninvasive ventilator and four interfaces were connected to IngMar ASL 5000 lung simulator. Meanwhile, the vibrating mesh nebulizer was connected to a ventilator circuit to simulate the nebulization during noninvasive ventilation. The nebulizer position was placed at proximal position (near the mask) and distal position (15 cm away from the mask); the inspiratory positive airway pressure (IPAP) and the expiratory positive airway pressure (EPAP) were set to 16/4, 16/8, 20/4, and 20/8 cmH2O, respectively. The aerosol was collected through a disposable filter placed between the simulated lung and the mask, after which the aerosol delivery was calculated. Meanwhile, we recorded the inspiratory tidal volume and the mean inspiratory flow. Results: The aerosol delivery varied between 1.7% ± 0.0% and 21.1% ± 1.1%. Only when EPAP was set to 4 cmH2O, the statistical difference in aerosol delivery was observed between the two types of interface, and between different leak port locations (p < 0.01; p = 0.04, respectively). When IPAP/EPAP was set to 16/4 and 20/4 cmH2O, respectively, at different nebulizer positions, there was a statistical difference between the interface with the same type but different leak port locations and between the interface with same leak port location but different inner volumes (all p < 0.01). Also, there was a correlation between the aerosol delivery and interface volume (p < 0.01, R2 = 0.55; p < 0.01, R2 = 0.51, respectively), and between aerosol delivery and the intentional leak of interfaces (p < 0.01, R2 = 0.59; p < 0.01, R2 = 0.48, respectively). When EPAP was set to 4 and 8 cmH2O, respectively, the aerosol delivery of nebulizer distal position was significantly higher than that of proximal position (12.2% ± 5.0% vs. 9.1% ± 4.1%, p < 0.05; 2.5% ± 0. 5% vs. 2.1% ± 0.3%, p < 0.01, respectively). Conclusion: Interfaces have a significant effect on aerosol delivery during NIV. The interfaces with different inner volumes, intentional leak, and leak port location may all have an effect on aerosol delivery. The addition of a 15 cm tube between the nebulizer and the mask significantly increases the aerosol delivery.

The mineral dust-induced gene, mdig, regulates angiogenesis and lymphangiogenesis in lung adenocarcinoma by modulating the expression of VEGF-A/C/D via EGFR and HIF-1α signaling.

Mineral dust­induced gene (mdig) is a novel lung cancer­related oncogene. The aim of this study was to explore the effects of mdig on angiogenesis and lymphangiogenesis by vascular endothelial growth factor (VEGF) in lung adenocarcinoma. mdig­overexpressing A549, H1299 and 293T cells, mdig­silenced A549, human umbilical vein endothelial cells (HUVECs) and human lymphatic endothelial cells (HLECs) were cultured under normoxic and hypoxic conditions. Protein expression levels of mdig, epidermal growth factor receptor (EGFR), phospho(p)­EGFR Tyr1068, hypoxia­inducible factor­1α (HIF­1α), VEGF­A/C/D and VEGF­R1/R2/R3 were assessed using western blotting. mRNA expression levels of mdig, EGFR and HIF­1α were measured using RT­qPCR. Tube formation and xenograft tumor experiments were performed to examine the mechanism of mdig in angiogenesis and lymphangiogenesis. Protein expression levels of EGFR, HIF­1α and VEGF­A/C/D were significantly upregulated in cells cultured under hypoxic conditions compared with those cultured under normoxic conditions, whereas the levels of mdig were decreased. Protein expression levels of EGFR, p­EGFR and VEGF­A/R1/R2 were significantly increased in the mdig­overexpressing cells, whereas the levels of HIF­1α and VEGF­C/D/R3 were decreased compared with those in control cells, all of which were reversed in mdig­silenced cells. Tumor volumes and density of angiogenesis in the mdig­overexpressing group were significantly increased compared with those in the control group, whereas the density of lymphangiogenesis was decreased. No tumors formed in the mdig­silenced group after 3 weeks of assessment in vivo. Protein expression levels of EGFR, p­EGFR, VEGF­A and angiogenesis density were significantly reduced in the mdig­overexpressing cells treated with an EGFR inhibitor, whereas the levels of HIF­1α, VEGF­C/D and the lymphangiogenesis density were significantly increased in mdig­overexpressing cells treated with a HIF­1α agonist. All changes in protein expression were reversed in EGFR agonist and HIF­1α inhibitor treated mdig­silenced cells. In conclusion, mdig is an oxygen­sensitive protein that promotes tumor growth and angiogenesis by activating the EGFR/p­EGFR/VEGF­A/VEGF­R1/R2 pathway and inhibits lymphangiogenesis by blocking the HIF­1α/VEGF­C/D/VEGF­R3 pathway.

[The comparison of the value of end-tidal partial pressure of carbon dioxide after eupnoea and prolonged expiratory method in Department of Respiratory Medicine].

OBJECTIVE: To compare and discuss the value of end-tidal partial pressure of carbon dioxide (PETCO2) using eupnoea or prolonged expiratory method, and explore their application value in department of respiratory medicine. METHODS: One hundred and fourteen patients admitted to the Department of Respiratory Medicine of hospital received PETCO2 monitor, using either eupnoea or prolonged expiratory method, and blood gas analysis was performed thereafter. Then the patients were divided into different groups according to different arterial partial pressure of carbon dioxide (PaCO2) and diseases. PETCO2 using two methods were compared and performed correlation analysis with PaCO2 was performed. A group of 45 healthy volunteers were served as the control group. RESULTS: (1) In healthy volunteers, PETCO2 using eupnoea or prolonged expiratory method was (39.68±5.07) mm Hg (1 mm Hg=0.133 kPa), (40.68±3.25) mm Hg, respectively, and they showed a good correlation with PaCO2 [(40.44±2.70) mm Hg, r1=0.79, P1=0.02; r2=0.91, P2=0.04). (2) In 114 patients group, PETCO2 using eupnoea and prolonged expiratory method was (35.93±8.19) mm Hg, (40.69±10.71) mm Hg, respectively, and they showed a good correlation with PaCO2 [(42.90±12.62) mm Hg, r1=0.80, r2=0.86, both P<0.01). (3) Subgroup analysis according to different levels of PaCO2: in normal PaCO2 group (35-45 mm Hg, n=49), PETCO2 using eupnoea or prolonged expiratory method was (37.64±4.67) mm Hg, (38.25±5.03) mm Hg, respectively, and they showed a good correlation with PaCO2 [(39.30±3.10) mm Hg, r1=0.76, P1=0.61; r2=0.82, P2=0.65]; in low PaCO2 group (<35 mm Hg, n=26), PETCO2 by using eupnoea or prolonged expiratory method was (28.4±5.63) mm Hg, (31.3±5.47) mm Hg, respectively, and they showed a good correlation with PaCO2 [(31.27±5.47) mm Hg, r1=0.68, r2=0.87, both P<0.01]; in high PaCO2 group (45-60 mm Hg, n=27), PETCO2 by using eupnoea expiratory method [(37.07±5.04) mm Hg] showed a poor correlation with PaCO2 [(49.51±5.18) mm Hg, r=0.42, P=0.02), while PETCO2 using prolonged expiratory method [(46.61±3.75) mm Hg] showed a good correlation with PaCO2 [(49.51±5.18) mm Hg, r=0.81, P=0.01). In extremely high PaCO2 group (>60 mm Hg, n=12), PETCO2 using eupnoea or prolonged expiratory method [(51.37±11.25) mm Hg, (62.57±16.24) mm Hg] showed a good correlation with PaCO2 [(74.63±12.20) mm Hg, r1=0.80, P1=0.09; r2=0.82, P2=0.11]. (4) Subgroup analysis according to different diseases: in chronic obstructive pulmonary disease (COPD) group (n=31), large pleural effusion group (n=21), and interstitial pneumonia group (n=15), PETCO2 using eupnoea expiratory method [(44.62±12.70), (34.89±3.26), (34.82±4.51) mm Hg] showed a poor correlation with PaCO2 [(60.18±17.38), (38.02±3.66), (38.70±4.08) mm Hg, r1=0.87, P1<0.01; r2=0.23, P2=0.03; r3=0.56, P3=0.02], while PETCO2 using prolonged expiratory method [(55.63±16.27), (38.59±4.23), (37.81±4.23) mm Hg] showed a good correlation with PaCO2 [(60.18±17.38), (38.02±3.66), (38.70±4.08) mm Hg, r1=0.89, P1<0.01; r2=0.66, P2=0.02; r3=0.87, P3=0.01]. In pulmonary embolism group (n=16), the results of PETCO2 using eupnoea and prolonged expiratory method [(30.57±9.49) mm Hg, (32.90±8.57) mm Hg] showed a good correlation with PaCO2 [(36.50±4.59) mm Hg, r1=0.75, r2=0.76, both P<0.01]. CONCLUSIONS: In Department of Respiratory Medicine, PETCO2 can replace PaCO2, but among the patients with COPD, interstitial pneumonia, large pleural effusion, the results of PETCO2 measured with prolonged expiratory method could be closer to that of PaCO2 as compared with that of using eupnoea expiratory method. In cases with high levels of PaCO2, blood gas analysis should be executed. In pulmonary embolism patients, there was no difference between eupnoea and prolonged expiratory method, and the results were lower than that of PaCO2.