Heliox ventilation in older hypertensive ICU patients improves hemodynamics: A randomized controlled study

doi:10.21203/rs.3.rs-3999637/v1

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Heliox ventilation in older hypertensive ICU patients improves hemodynamics: A randomized controlled study

https://doi.org/10.21203/rs.3.rs-3999637/v1

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Background: Conventional mechanical ventilation has adverse impacts on hemodynamics of older hypertensive ICU patients. Limited studies have addressed way to ameliorate these negative effects. This study aimed at determining if heliox ventilation mitigated the side-effects of conventional mechanical ventilation in senile hypertensive patients.

Methods: Seventy-nine older adults aged 65 to 95 years with essential hypertension who underwent invasive mechanical ventilation treatment, were divided into two groups: a control group of nitrogen-oxygen ventilation (n = 40) and an experimental group of heliox ventilation (n = 39). The control group received conventional room air ventilation and the experimental group innovatively adopted the closed heliox ventilation technique. All patients had appropriate positive end-expiratory pressure (PEEP) values (5-8cmH₂O) using the optimal oxygenation method under VCV mode throughout the study. Blood pressure, central venous pressure (CVP), central venous oxygen saturation (ScvO₂), heart rate (HR), and airway pressure were measured every hour.

Results: An increase of CVP and airway pressure coupled with a decrease of blood pressure and ScvO₂ were observed in the control group as expected (p < 0.05). Comparatively, CVP and airway pressure reductions with an increased ScvO₂were observed in the experimental group (p < 0.05). In the experimental group, blood pressure and HR did not change significantly.

Conclusions: Heliox ventilation improves cardiac function and blood pressure in older hypertensives as compared with nitrogen-oxygen ventilation.

Trial registration

This trial was registered. The Chinese trial registration number is ChiCTR2100043945. The date of registration is 6-3-2021. The registered name is that heliox ventilation improves hemodynamics in older patients with hypertention admitted to the intensive care unit.

Helium-oxygen inhalation

Positive-pressure ventilation

Cardiac function

Blood pressure

older patients with hypertension

The number of older patients with essential hypertension is increasing promptly year by year worldwide [1]. Recent data from the National Health and Nutrition Examination Survey indicate that 70% of older adults have hypertension [2]. Elastic arteries of older hypertensives dilate and stiffen. The result is stiff arteries that have decreased capacitance and limited recoil making them unable to accommodate the changes that occur during the cardiac cycle [3]. If the cardiac output decreases, blood pressure drops immediately in older hypertensives.

There are many methods for measurement of cardiac output. Traditional cardiac function assessment methods, such as pulmonary artery catheter and pulse indicator continous cadiac output, are invasive and expensive [4]. Echocardiographic examination is non-invasive, but postural position, mechanical ventilation gas interference, and physician skill level make for varying results [5]. All of these methods have shortcomings and limited use in clinical studies. Another important factor for hemodynamic stability is the balance between oxygen delivery (DO₂) and consumption (VO₂). The most often used bedside parameter to assess the relationship between oxygen supply and consumption is central venous oxygen saturation (ScvO₂). Its value decreases in conditions with low oxygen supply such as in the presence of low cardiac output, decreased hemoglobin, and decreased arterial oxygen saturation. In cases of increased oxygen demand such as shivering, fever, agitation, and hypermetabolic state, its value also decreases [6]. So if hemoglobin, arterial oxygen saturation, and oxygen demand are relatively invariant, ScvO₂ is positively associated with cardiac output. Recent studies have found that ScvO₂ can be used to evaluate the condition of left cardiac ejection, which is simple and reliable, making it great for use in clinical applications [7-9]. As such, this study used ScvO₂ to reflect left cardiac ejection.

The elasticity of arterial vessels in older patients with hypertension is diminished, and the adjustment function of arterial vessels is poor as well. Therefore, hemodynamics is more susceptible to external factors such as positive pressure ventilation. Preliminary studies have found positive end expiratory pressure（PEEP）above 4 cmH₂O, in hypertensive patients a decrease of blood pressure and ScvO₂ with an increase of heart rate（HR）, indicating decreased cardiac output [10]. However, for older hypertensive patients with acute respiratory distress syndrome and other respiratory diseases, high PEEP treatment is necessary because it can prevent end-of-expiratory alveolar collapse, reduce alveolar exudation, and improve lung compliance [11]. In view of the many advantages of high PEEP, hemodynamic abnormalities caused by it are still difficult to overcome. Limited studies have addressed how to ameliorate these negative impacts. Hence, the exploration of heliox to reduce the effects of positive pressure ventilation on hemodynamics in older patients with hypertension is necessary.

Heliox, a mixture of helium and oxygen, has a density that is less than that of air. Breathing heliox leads to a reduction in resistance to flow within the airways [12]. The study of Truebel H showed that healthy volunteers who underwent heliox ventilation had reduced variations in blood pressure caused by mechanical ventilation along with more stable hemodynamics overall [13]. Whether heliox can reduce high intrapleural pressures and improve hemodynamics while preserving lung tissue is not well understood, especially in older hypertensives.

In this research, whether heliox ventilation, as compared to nitrogen-oxygen ventilation, could lessen the effects of positive-pressure ventilation on blood pressure and heart function in senile hypertensive patients was investigated, so as to minimize adverse impacts of conventional mechanical ventilation on hemodynamics.

Study design

For all selected patients, the VCV ventilator mode (Vela ventilator, American) was utilized to assist breathing. Tidal volume (8 ml/kg), PEEP (Optimal oxygenation method setting at 5-8 cmH₂O), I/E (1:2), and respiratory frequency (18 times/min) were controlled to maintain pulmonary oxygenation and promote carbon dioxide exhalation, that is nitrogen-oxygen ventilation. If an oxygen concentration maintenance of 40% made the peripheral oxygen saturation more than 95%, the patient was admitted to the study. All patients underwent radial arterial puncture and subclavian venous catheter. Phlegm was removed from the airway, and subjects were placed at a comfortable 30° half supine position with an infusion speed regulated at 40–50 drops/min. Midazolam 0.05 mg/kg/h and Remifentanil 0.05-0.08 µg/kg/min were used to limit spontaneous breathing. Subjects underwent helium-oxygen or nitrogen-oxygen ventilation for 3h according to their groups. Tidal volume and PEEP were maintained relatively constant, and changes in blood pressure, central venous pressure (CVP), ScvO₂, HR, plasma lactic acid (Lac), and airway pressure were measured at different timepoints. Both the control and experimental groups were mechanically ventilated, so researchers were blind to patient treatment conditions. The indicator observer did not know whether it was the experimental group or the control group when collecting data. If a significant decrease in blood pressure and an obvious decrease of peripheral oxygen saturation (SpO₂) were noted, the study was terminated to ensure patient safety. No patients withdrew from the study. We have used the CONSORT reporting guidelines, and cited them as: Schulz KF, Altman DG, Moher D, for the CONSORT Group. CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials.

Participants

This randomized controlled study was conducted between October 2020 and January 2023 at the Intensive Care Unit in Fujian Medical University Union Hospital. The Chinese clinical trial registration number is ChiCTR2100043945. Seventy-nine older adults aged 65 to 95 years with essential hypertension and respiratory failure undergoing invasive mechanical ventilation treatment were divided into two groups, a control group of nitrogen-oxygen ventilation (n = 40) and an experimental group of heliox ventilation (n = 39) (Fig. 1). The computer randomly generated treatment assignments corresponding to numbers 01-79 were divided into a nitrogen-oxygen ventilation group (n = 40) and a heliox ventilation group (n = 39). Respiratory failure in these 79 older hypertensives resulted from pneumonia. All patients or their legally authorized representatives provided written informed consent. The study was approved by the Ethics Committee of Union Hospital Affiliated to Fujian Medical University. Patients with secondary hypertension, shock, arrhythmia, severe heart failure (NYHA cardiac function grade III - IV), vasoactive drug use, or lung malignant tumors were excluded.

Implementation of heliox ventilation

It was realized that introducing helium to the anesthetic machine improved patient breathing characteristics. First, the air flow of the anesthetic machine (Drag, Germany) was adjusted to zero, then helium gas was connected to the nitrous oxide pathway. Before the experiment began, the anesthetic machine was connected to simulated lungs for pure oxygen ventilation for about 30 minutes, and helium gas was continuously introduced into the circuit to drain the nitrogen gas. The oxygen concentration measuring instrument was connected to the air supply end of the anesthetic machine, keeping the total flow of helium and oxygen gas constant. The flow of helium and oxygen gas was constantly adjusted to maintain an oxygen concentration of 40%. Finally, the anesthetic machine was connected to the patient (Fig. 2).

Lung function and hemodynamic measurements

To ensure the subclavian vein catheter (Arrow, American) was located in the superior vena cava, the position of the catheter was confirmed by bedside X-ray or CT. The subclavian vein catheter was connected to a multi-parameter cardiac monitor (GEcicpro/8000i, American) to measure CVP. Extraction of 1.0 ml central venous catheter blood was used for blood gas analysis (i-stat300 blood gas analyzer, Abbott, United States), as well as ScvO₂ and Lac monitoring. In addition, a multi-parameter cardiac monitor continuously assessed radial blood pressure, HR, and SpO₂. A ventilator or an anesthetic machine continuously monitored peak airway pressure (Ppeak), platform airway pressure (Pplat), driving pressure (∆P), tidal volume (VT), and minute ventilation volume (MV). The above indexes were measured at 0,1,2,3 hours of ventilation.

Evaluation criteria

Hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg under sufficient sedation during mechanical ventilation without man-machine confrontation and/or the self-reported use of antihypertensive medication in the previous two weeks [14].

Statistics analysis

The sample size for the study was determined using statistical analysis software, NCSS PASS. The primary outcome measure was ScvO₂. According to the Two-Sample T-Tests sample size calculation method, with α=0.05 and 1-β=0.9 test level, a test was performed according to 1:1 grouping, 68 patients need to be included, 34 cases in each group, taking into account the shedding rate of about 10%, at least 76 patients were included, each group 38 cases. When 20 cases were collected in each of the experimental and control groups, changes in the main index ScvO₂ were tracked, and the differences in changes in ScvO₂ between the two groups were compared using repeated-measures ANOVA to confirm clinical significance. This study was stopped only when the sample size was fully collected. SPSS 24.0 software was used for statistical analysis of the data. All data were presented as mean ± SD or median (interquartile range) as indicated by data distribution tested by the Shapiro-Wilk test. To compare data between groups, a Student’s t-test, analysis of variance (ANOVA), Chi-square test, Mann–Whitney test, or Kruskal–Wallis test was utilized depending on their distribution and number of variables. Correlation was analyzed by Pearson correlation analysis. Confounding factors were controlled by multiple linear regression or logistic regression analysis. Statistical significance was considered at p < 0.05.

Participants characteristics

Descriptive characteristics are summarized in Supplementary eTable 1. There were no statistically significant differences in sex, age, serum creatinine (Scr), uric acid (UA), triglycerides (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), hemoglobin (HB), or body temperature (T) between the two groups (p > 0.05). Before starting heliox or nitrogen-oxygen ventilation, there was also no statistically significant difference in SBP, DBP, mean arterial blood pressure (MABP), CVP, Lac, or SpO₂ between the groups (p > 0.05). There were five patients with coronary atherosclerotic heart disease, one patient with chronic pulmonary heart disease, five patients with essential hypertensive heart disease, and 29 patients without basic heart disease in the control group. There were three patients with coronary atherosclerotic heart disease, four patients with chronic pulmonary heart disease, five patients with essential hypertensive heart disease, and 27 patients without basic heart disease in the experimental group. There was no significant difference in the results of basic heart disease between the two groups (Fisher's exact test: p = 0.586). Also, there were three patients with chronic obstructive pulmonary disease, two patients with bronchiectasis, and 35 patients without basic pulmonary disease in the control group. There were eight patients with chronic obstructive pulmonary disease, no patients with bronchiectasis, and 31 patients without basic pulmonary disease in the experimental group. There was no significant difference in the results of basic pulmonary disease between the two groups (Fisher's exact test: p = 0.098).

Results per study group

Effect of different ventilation modes on blood pressure

Based on the results of Mauchly sphericity test (p < 0.05), the data did not conform to sphericity assumptions. Therefore, ANOVA with repeated measures was used, and the Greenhouse-Geisser correction was applied. The results of the ANOVA with repeated measures showed that after correcting for the within-subjects factor (p < 0.05), there was a significant difference in the mean SBP, DBP, and MABP at different time points. Furthermore, the interaction between the ventilation group and treatment time was significant (p < 0.05), indicating that the ventilation group had an effect on the measurements. Specifically, the overall mean of SBP, DBP, and MABP differed significantly between the two ventilation groups (p < 0.05), as shown in Fig 3, Supplementary eTable 3-5. Moreover, in the control group, ventilation time was negatively correlated with SBP (r = -0.264, p = 0.001), DBP (r = -0.188, p = 0.017), and MABP (r = -0.257, p = 0.001). With an increase in controlling factors, a negative correlation between ventilation time and SBP, DBP as well as MABP were still observed (Supplementary eTable 12). But there was no significant change in SBP, DBP and MABP during ventilation in the experimental group (p > 0.05) (Supplementary eTable 2).

Effect of different ventilation modes on cardiac function

After applying the Greenhouse-Geisser correction, the results of the repeated measures ANOVA for CVP showed that the overall means at different times were not equal, with a corrected p-value of < 0.05. Moreover, the interaction between the ventilation group and treatment time was significant, with a corrected p-value of < 0.05. This finding indicates that the ventilation group had an effect on the CVP measurements, and that there was an interaction between the ventilation group and treatment time. The overall mean of CVP was also found to be significantly different between the two ventilation groups, with a p-value of < 0.05 (Fig 4, Supplementary eTable 6). Moreover, in the control group, ventilation time was positively correlated with CVP (r = 0.232, p = 0.003). With an increase in controlling factors, a positive correlation between ventilation time and CVP was still observed (Supplementary eTable 13). In the experimental group, ventilation time was negatively correlated with CVP (r = -0.536, p < 0.001). With an increase in controlling factors, a negative correlation between ventilation time and CVP was still observed (Supplementary eTable 13).

Using the Greenhouse-Geisser method, the results of ANOVA of repeated measurements of ScvO₂, after correction for the internal factor, showed a p-value of > 0.05, indicating no statistical significance in the overall means of ScvO₂ at different times. However, the interaction between the ventilation group and treatment time, after correction, had a p-value of < 0.05, suggesting that there was an interaction between ventilation group and treatment time, and that the ventilation group had an effect on the measurements. Furthermore, the overall mean of ScvO₂ was found to be significantly different between the two ventilation groups, with a p-value of < 0.05 (Fig 4, Supplementary eTable 7). Moreover, in the control group, ventilation time was negatively correlated with ScvO₂ (r = -0.378, p < 0.001). Using multiple linear regression analysis to control confounding factors, the correlation between ventilation time and ScvO₂ still existed (Supplementary eTable 14). In the experimental group, ventilation time was positively correlated with ScvO₂ (r = 0.257, p = 0.001). With an increase in controlling factors, a positive correlation between ventilation time and ScvO₂ was still observed (Supplementary eTable 14).

Using the Greenhouse-Geisser method, the results of ANOVA of repeated measurements of HR, after correction of the sphericity assumption (Mauchly's test, p < 0.05), indicated that the overall means of HR at different times were not the same. The interaction between ventilation group and treatment time was statistically significant (interaction time×ventilation group corrected, p < 0.05), indicating that ventilation group had an effect on the measurements. However, there was no significant difference in the overall mean of HR between the two ventilation groups (p > 0.05, Fig 4, Supplementary eTable 8). Furthermore, in both groups, Lac and SpO₂ did not change significantly during ventilation (p > 0.05) (Supplementary eTable 2).

Effects of different ventilation modes on airway pressure

In both groups, VT and MV were unaffected by ventilation time (p > 0.05) (Supplementary eTable 2). After applying the Greenhouse-Geisser correction, the results of ANOVA of repeated measurements for Ppeak, Pplat and ∆P showed that the overall means of Ppeak, Pplat and ∆P at different times were significantly different (p < 0.05). The interaction between ventilation group and treatment time was also significant (p < 0.05), indicating that ventilation group had an effect on the measurements. Specifically, the overall mean of Ppeak was significantly different for the two ventilation groups (p < 0.05, Fig 5, Supplementary eTable 9), while there was no statistical significance in the overall mean of Pplat and ∆P between the two ventilation groups (p > 0.05, Fig 5, Supplementary eTable 10). In addition, in the control group, ventilation time was positively correlated with the Ppeak (r = 0.194, p = 0.014), Pplat (r = 0.184, p = 0.020) and ∆P (r = 0.184, p = 0.020) . On the contrary, in the experimental group, ventilation time was negatively correlated with Ppeak (r = -0.337, p < 0.001), Pplat (r = -0.312, p < 0.001) and ∆P (r = -0.312, p < 0.001) . In both groups, using multiple linear regression analysis to control confounding factors, a correlation between ventilation time and airway pressure was still observed (Supplementary eTable 15-17).

PEEP is applied during the end of expiration to maintain alveolar pressure above atmospheric pressure. The benefit of PEEP has been demonstrated in terms of preventing collapsed alveoli and improving oxygenation [15, 16]. However, previous studies have found that applying relatively high PEEP affects hemodynamics via complex mechanisms, especially for older hypertensives [10]. PEEP has many advantages, but there is no effective solution to its adverse effect on hemodynamics. This study investigated the effect of heliox ventilation on hemodynamics in older patients with hypertension at relatively high PEEP levels compared with conventional nitrogen-oxygen ventilation. The results showed that when PEEP was adjusted to 5-8 cm H₂O, in the nitrogen-oxygen ventilation group, blood pressure of older hypertensives decreased with the prolongation of ventilation time and then tended to be stable. However, in the heliox ventilation group, there was no significant change in blood pressure with prolonged ventilation time. Because of diminished elasticity in older hypertensives’ blood vessels and subsequent functional decline [17], positive-pressure ventilation would be a negative influence on hemodynamics, but these observations suggest that heliox ventilation can reduce this adverse effect.

To further study why heliox ventilation results in more stable blood pressure in older hypertensives at relatively high PEEP levels，the effect of heliox ventilation on cardiac function in older hypertensives with mechanical ventilation was explored. As lung volume status was of high importance for hemodynamic instability in patients ventilated with positive-pressure, a sedative drug called midazolam and an analgesic drug called Remifentanil were used to minimize spontaneous breathing, and tidal volume was maintained relatively constant in this study. Moreover, prior to the study, there was no statistically significant differences in blood pressure, CVP, or Lac between the experimental and control groups. This is indicative of the similar initial hemodynamic status between the two groups. During this study patients’ body position and infusion speed were controlled to ensure similar fluid intake. It was found that in both groups, VT, MV, PEEP, SpO₂, and Lac were unaffected by ventilation time. These are indicators that the lung volume status and microcirculation perfusion of the two groups were stable during the study.

In this study, with prolonged ventilation time, an increase of CVP, airway pressure with a decrease of ScvO₂were observed in the control group, but a decrease of CVP and airway pressure with an increase of ScvO₂ were observed in the experimental group. A correlation between CVP, ScvO₂, airway pressure, and ventilation time existed in the two groups. This indicates that heliox ventilation improves cardiac function in older hypertensives at a relatively high level of PEEP compared with nitrogen-oxygen ventilation.

In general, the increase in PEEP caused higher airway pressure which resulted in increased intrathoracic pressure (ITP) [18]. Elevation of CVP by increasing ITP resulted in a reduction in venous return [19]. In older hypertensive patients, the thickened and stiffened vein walls caused slower venous return than that of non-hypertensive subjects, which resulted in reduced right ventricular (RV) preload [20]. Moreover high PEEP led to increased end inspiratory lung volume, which was responsible for the RV afterload and reduced flow through the lung [21, 22]. As a result, the reduction in RV ejection caused by PEEP decreased left ventricular filling in hypertensives [23]. Therefore, the increase in PEEP led to a decrease of blood pressure and ScvO₂ in hypertensives. With low density and high diffusion, heliox can reduce the occurrence of turbulence in the airway and effectively reduce the airway resistance, subsequently reducing endogenous PEEP and lung volume. In this way, venous return and pulmonary circulation resistance can be relatively stable, and hemodynamic status can be improved to a certain extent [24-26]. Therefore in this study, compared with nitrogen-oxygen ventilation at a relatively high PEEP level, heliox ventilation reduced airway pressure and CVP and increased ScvO₂ in older hypertensive patients, without affecting heart rate or causing significant fluctuations in blood pressure. Heliox ventilation improves cardiac function and blood pressure in older hypertensives at a relatively high level of PEEP compared with nitrogen-oxygen ventilation.

Heliox ventilation may improve hemodynamics in older patients with hypertension at a relatively high level of PEEP through other mechanisms as well. In a previous study, this research group adopted the rabbit acute lung injury (ALI) model and found that heliox ventilation reduced the inflammatory exudation in blood vessels and alveolar cavities of lung tissue, and increased the blood perfusion of lung tissue [27, 28]. It was speculated that heliox ventilation might further stabilize hemodynamics by improving pulmonary circulation. Besides, Pagel and Smit's study suggested that heliox ventilation could improve organ perfusion through the nitric oxide pathway [29, 30]. In 2018, Smit KF found that heliox treatment of human umbilical vein endothelial cells (HUVECs) resulted in changes in cytoskeleton structure, thus maintaining the stability of endothelial membrane and reducing vascular permeability [31]. In 2019, another study by Smit KF found that plasma of healthy volunteers breathing heliox protected HUVECs against hypoxic cell damage [32]. Therefore, it was concluded that heliox ventilation might improve pulmonary circulation by regulating pulmonary vasoactive factors and protecting pulmonary vascular endothelial cells, thus stabilizing hemodynamics in older patients with hypertension on mechanical ventilation. This needs to be further proved by follow-up research.

Heliox is difficult to prepare, expensive, and easy to escape from tightly sealed containers due to its high diffusion, resulting in high therapeutic cost and limited clinical application [25]. In this study, the hermetic breathing circuit was innovatively applied for heliox ventilation to recycle helium gas. The service time of 40 L high purity helium gas was extended from 15 min to at least 30 h, which greatly reduced the treatment cost and facilitated the application of heliox ventilation technology in clinical practice, with good economic benefits and clinical practical value. However, this study also had some shortcomings. Since the change of intrathoracic pressure in patients with mechanical ventilation largely determines the stability of hemodynamics, it is better to measure dynamic esophageal pressure during the study to more intuitively reflect the change of intrathoracic pressure. However, as most of the patients and their families refused this examination, esophageal pressure measurement could not be carried out during the study. Therefore, in the process of this study, sedation and analgesia were used to suppress spontaneous respiration and tidal volume was controlled to minimize the influencing factors and ensure the accuracy of the study.

In older hypertensives with mechanical ventilation, this study shows that heliox ventilation reduced the adverse effects of positive-pressure on hemodynamics. However, due to the limited patient source, the effects of heliox ventilation on hemodynamics in older hypertensives with mechanical ventilation should be confirmed by a large sample multicenter clinical study.

Positive-pressure ventilation have many advantages but can significantly affect the hemodynamic status of older patients with hypertension. A closed heliox ventilation technique with helium recycling can improve cardiac function and stabilize hemodynamics in older hypertensives with mechanical ventilation, at a greatly reduced treatment cost. This heliox ventilation technique can be effectively applied to older patients with hypertension complicated with respiratory failure who are susceptible to significant fluctuations in hemodynamics caused by positive pressure ventilation, which is worthy of clinical application.

PEEP: positive end expiratory pressure

ScvO₂: central venous oxygen saturation

CVP: central venous pressure

DO₂: oxygen delivery

VO₂: consumption

HR: heart rate

Lac: plasma lactic acid

SpO₂: peripheral oxygen saturation

Ppeak: peak airway pressure

Pplat: platform airway pressure

∆P: driving pressure

VT: tidal volume

MV: minute ventilation volume

SBP: systolic blood pressure

DBP: diastolic blood pressure

ANOVA: analysis of variance

MABP: mean arterial blood pressure

Scr: serum creatinine

UA: uric acid

TG: triglyceride

TC: total cholesterol

LDL-C: low density lipoprotein cholesterin

FPG: fasting plasma glucose

HB: hemoglobin

T: body temperature

ITP: increased intrathoracic pressure

RV: right ventricular

ALI: acute lung injury

HUVECs: human umbilical vein endothelial cells

Ethics approval and consent to participate

All patients or their legally authorized representatives provided written informed consent. The study was approved by the Ethics Committee of Union Hospital Affiliated to Fujian Medical University. The committee’s reference number was 2020WSJK002. Chinese clinical trial registration number is ChiCTR2100043945. All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Consent for publication

Not applicable

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. All data generated during the project will be made freely available via the ResMan Research Manager (ChiCTR2100043945) and Union Hospital, Fujian Medical University’s Research Data Repository. DOIs to these data will be provided (as part of the DataCite programme) and cited in any published articles using these data and any other data generated in the project. There are no security, licensing, or ethical issues related to these data.

Competing interests

The authors have no conflict of interest regarding the publication of this paper.

Funding resources

This work was supported by Science and Technology Guiding Project for Social Development of Fujian Science and Technology Plan in 2022 (Appropriation No.2022Y0020) and National Clinical Key Specialty Project of Geriatrics (Appropriation No.212790530603).

Authors' Contributions

LZ designed the experiment, conducted the experiment, analyzed the data and wrote the manuscript. LC designed the experiment, conducted the experiment and wrote the manuscript. JL investigated the patients and collected the data. MZ investigated the patients and analyzed the data. HZ and QW designed the experiment, funded the study and wrote the manuscript. All authors have read the final submitted version and approved the submission.

Acknowledgments

We would like to thank all of our colleagues who recruited and treated the patients. This study was supported by Fujian Science and Technology Project and National Clinical Key Specialty Project of Geriatrics.

Sheppard JP, Burt J, Lown M, et al. Effect of antihypertensive medication reduction vs usual care on short-term blood pressure control in patients with hypertension aged 80 years and older: the OPTIMISE randomized clinical trial. JAMA. 2020; 323(20): 2039-2051. doi: 10.1001/jama.2020.4871.
Virani SS, Alonso A, Aparicio HJ, et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association. Circulation. 2021; 143(8): e254-e743. doi: 10.1161/CIR.0000000000000950.
Schaafs LA, Tzschätzsch H, Reshetnik A, et al. Ultrasound Time-Harmonic Elastography of the Aorta: Effect of Age and Hypertension on Aortic Stiffness. Invest Radiol. 2019; 54(11): 675-680. doi: 10.1097/RLI.0000000000000590.
Fortuni F, Tavazzi G, De Ferrari GM. Pulmonary Artery Catheter in Cardiogenic Shock: Will the Benefits Finally Outweigh the Costs and Complications? JACC Heart Fail. 2021; 9(4): 322-323. doi: 10.1016/j.jchf.2020.12.007.
Galea N, Bandera F, Lauri C, Autore C, Laghi A, Erba PA. Multimodality Imaging in the Diagnostic Work-Up of Endocarditis and Cardiac Implantable Electronic Device (CIED) Infection. J Clin Med. 2020; 9(7): 2237. doi: 10.3390/jcm9072237.
Khalil MH, Sekma A, Zhani W, Zorgati A, Ben Soltane H, Nouira S, GREAT Network. Variation in central venous oxygen saturation to assess volume responsiveness in hemodynamically unstable patients under mechanical ventilation: a prospective cohort study. Crit Care. 2021; 25(1): 245. doi: 10.1186/s13054-021-03683-6.
Lanspa MJ, Pittman JE, Hirshberg EL, et al. Association of left ventricular longitudinal strain with central venous oxygen saturation and serum lactate in patients with early severe sepsis and septic shock. Crit Care. 2015; 19: 304. doi: 10.1186/s13054-015-1014-6.
Xu B, Yang X, Wang C, et al. Changes of central venous oxygen saturation define fluid responsiveness in patients with septic shock: A prospective observational study. J Crit Care. 2017; 38: 13-19. doi: 10.1016/j.jcrc.2016.09.030.
Zhang H, Chan L, Meyring-Wösten A, et al. Association between intradialytic central venous oxygen saturation and ultrafiltration volume in chronic hemodialysis patients. Nephrol Dial Transplant. 2018; 33(9): 1636-1642. doi: 10.1093/ndt/gfx271.
Zhou L, Cai G, Xu Z, Weng Q, Ye Q, Chen C. High positive end expiratory pressure levels affect hemodynamics in older patients with hypertension admitted to the intensive care unit: a prospective cohort study. BMC Pulmonary Medicine. 2019; 19(1): 224. doi: 10.1186/s12890-019-0965-9.
Sarge T, Baedorf-Kassis E, Banner-Goodspeed V, et al. EPVent-2 Study Group. Effect of Esophageal Pressure-Guided Positive End-Expiratory Pressure on Survival from Acute Respiratory Distress Syndrome: A Risk-Based and Mechanistic Reanalysis of the EPVent-2 Trial. Am J Respir Crit Care Med. 2021; 204(10): 1153-1163. doi: 10.1164/rccm.202009-3539OC.
Jolliet P, Ouanes-Besbes L, Abroug F, et al. E.C.H.O. ICU Trial Investigators. A Multicenter Randomized Trial Assessing the Efficacy of Helium/Oxygen in Severe Exacerbations of Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2017; 195(7): 871-880. doi: 10.1164/rccm.201601-0083OC.
Truebel H, Wuester S, Boehme P, et al. A proof-of-concept trial of HELIOX with different fractions of helium in a human study modeling upper airway obstruction. Eur J Appl Physiol. 2019; 119(5): 1253-1260. doi: 10.1007/s00421-019-04116-7.
Tschanz CMP, Cushman WC, Harrell CTE, Berlowitz DR, Sall JL. Synopsis of the 2020 U.S. Department of Veterans Affairs/U.S. Department of Defense Clinical Practice Guideline: The Diagnosis and Management of Hypertension in the Primary Care Setting. Ann Intern Med. 2020; 173(11): 904-913. doi: 10.7326/M20-3798.
Garnero A, Tuxen D, Corno G, Durand-Gasselin J, Hodgson C, Arnal JM. Dynamics of end expiratory lung volume after changing positive endexpiratory pressure in acute respiratory distress syndrome patients. Crit Care. 2015; 19(1): 340. doi: 10.1186/s13054-015-1044-0.
Bastia L, Engelberts D, Osada K, et al. Role of Positive End-Expiratory Pressure and Regional Transpulmonary Pressure in Asymmetrical Lung Injury. Am J Respir Crit Care Med. 2021; 203(8): 969-976. doi: 10.1164/rccm.202005-1556OC.
Sims KD, Smit E, Batty GD, Hystad PW, Odden MC. Intersectional Discrimination and Change in Blood Pressure Control among Older Adults: The Health and Retirement Study. J Gerontol A Biol Sci Med Sci. 2022; 77(2): 375-382. doi: 10.1093/gerona/glab234.
Sahetya SK, Goligher EC, Slutsky AS. Searching for the Optimal PEEP in Patients Without ARDS: High, Low, or in Between? JAMA. 2020; 324(24): 2490-2492. doi: 10.1001/jama.2020.23067.
Pinsky Michael R. My paper 20 years later: Effect of positive end-expiratory pressure on right ventricular function in humans. Intensive Care Med. 2014; 40(7): 935-41. doi: 10.1007/s00134-014-3294-8.
Orde SR, Behfar A, Stalboerger PG, Barros-Gomes S, Kane GC, Oh JK. Effect of positive end-expiratory pressure on porcine right ventricle function assessed by speckle tracking echocardiography. BMC Anesthesiol. 2015; 15: 49. doi: 10.1186/s12871-015-0028-6.
Vieillard-Baron A, Matthay M, Teboul JL, et al. Experts' opinion on management of hemodynamics in ARDS patients: focus on the effects of mechanical ventilation. Intensive Care Med. 2016; 42(5): 739-749. doi: 10.1007/s00134-016-4326-3.
Protti A, Andreis DT, Monti M, et al. Lung stress and strain during mechanical ventilation: any difference between statics and dynamics? Crit Care Med. 2013; 41(4): 1046-55. doi: 10.1097/CCM.0b013e31827417a6.
Alviar CL, Miller PE, McAreavey D, et al.ACC Critical Care Cardiology Working Group. Positive Pressure Ventilation in the Cardiac Intensive Care Unit. J Am Coll Cardiol. 2018; 72(13): 1532-1553.doi: 10.1016/j.jacc.2018.06.074.
Lee DL, Lee H, Chang HW, Chang AY, Lin SL, Huang YC. Heliox improves hemodynamics in mechanically ventilated patients with chronic obstructive pulmonary disease with systolic pressure variations. Crit Care Med. 2005; 33(5): 968-73. doi: 10.1097/01.ccm.0000163403.42842.fe.
Wu W, Chen X, Liu X, Liu C, Lu G. Heliox-driven nebulization has a positive effect on the lung function in lipopolysaccharide-induced chronic obstructive pulmonary disease rat model. Med Sci Monit. 2016; 22: 4100-4106. doi: 10.12659/msm.896736.
Levy SD, Alladina JW, Hibbert KA, Harris RS, Bajwa EK, Hess DR. High-flow oxygen therapy and other inhaled therapies in intensive care units. Lancet. 2016; 387(10030): 1867-78. doi: 10.1016/S0140-6736(16)30245-8.
Chen DM, Weng QY. Effects of Helium-Oxygen Mechanical Ventilation on Inflammation and Lung Cell Apoptosis in Rabbits with Acute Lung Injury. Chinese Journal of Clinical Medicine. 2013; 20(6): 751-754,758. doi: CNKI:SUN:LCYX.0.2013-06-002.
You HP, Zhang XN, Weng QY. Effects of mechanical ventilation with heliox-oxygen on acute lung injury in rabbits. Chinese Journal of Anesthesiology. 2015; 35(8): 948-950. doi: 10.3760/cma.j.issn.0254-1416.2015.08.010.
Pagel PS, Krolikowski JG, Pratt PF Jr, et al. The mechanism of helium-induced preconditioning: a direct role for nitric oxide in rabbits. Anesth Analg. 2008; 107(3): 762-8. doi: 10.1213/ane.0b013e3181815995.
Smit KF, Oei GT, Brevoord D, et al. Helium induces preconditioning in human endothelium in vivo. Anesthesiology. 2013; 118(1): 95-104. doi: 10.1097/ALN.0b013e3182751300.
Smit KF, Konkel M, Kerindongo R, et al. Helium alters the cytoskeleton and decreases permeability in endothelial cells cultured in vitro through a pathway involving Caveolin-1. Sci Rep. 2018; 8(1): 4768. doi: 10.1038/s41598-018-23030-0.
Smit KF, Oei GTML, Konkel M, et al. Plasma from volunteers breathing helium reduces hypoxia-induced cell damage in human endothelial cells-mechanisms of remote protection against hypoxia by helium. Cardiovasc Drugs Ther. 2019; 33(3): 297-306. doi: 10.1007/s10557-019-06880-2.

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Heliox ventilation in older hypertensive ICU patients improves hemodynamics: A randomized controlled study

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