# Efficacy Evaluation of High-Volume Hemofiltration in Patients with Severe Acute Respiratory Distress Syndrome

Authors: Yonglei Zhang; Yan Zhang; Jiming Pan
Journal: Evidence-Based Complementary and Alternative Medicine
 (2022)

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## Abstract

Objective. To investigate the efficacy of high-volume hemofiltration (HVHF) in the treatment of severe acute respiratory distress syndrome (ARDS) caused by sepsis and its effect on serum levels of miR-126, miR-184, and MAP1-LC3. Methods. From July 1, 2015 to December 31, 2021, patients with severe ARDS caused by sepsis who were admitted to our hospital were retrospectively analyzed. Patients who received conventional treatment were summarized into the control group, and those who received HVHF were summarized into the study group. The treatment effects of the two groups were compared. Results. Ninety-five qualified patients were retrieved, with 42 patients in the control group and 53 patients in the study group. After treatment, the levels of IL-6, IL-10, TNF-α, miR-126, miR-184, and MAP1-LC3 were significantly lower in the study group (P<0.05 for all), whereas PEF, FRC, TEF25%, heart rate, mean arterial pressure, and blood oxygen were significantly higher in the study group (P<0.05 for all). Conclusion. HVHF has a good clinical effect on improving patients with severe ARDS caused by sepsis and can improve the pulmonary function of patients.


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## Body

## 1. Introduction

Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is characterized by a high mortality rate and is commonly seen in intensive care units [1, 2]. The pathogenesis of acute respiratory distress syndrome (ARDS) is caused by acute events, which can cause damage to the capillaries and epithelial cells in the lung, thereby causing diffuse edema of the lung tissue that leads to acute hypoxic respiratory failure. In recent years, anti-infection and multiorgan support technologies have made great progress, but the mortality rate of sepsis is still high [3]. High-volume hemofiltration (HVHF) technology has been shown to remove inflammatory mediators in blood purification technology, enhance antigen presentation, leukocyte activity, and body immunity, and can significantly improve lung function and blood oxygen concentration in ARDS patients [4]. This study aims to investigate the clinical effect of continuous HVHF in patients with severe ARDS.


## 2. Materials and Methods

### 2.1. General Information

From July 1, 2015 to December 31, 2021, patients with severe ARDS caused by sepsis who were treated in our hospital were retrospectively analyzed. All patients in this study signed the informed consent form. This study was approved by the Institutional Ethical Committee of our hospital.Inclusion criteria were as follows: the clinical diagnosis was severe ARDS caused by sepsis [3]; severe hypoxia PaO2/Fi O2 ≤ 100 mm·Hg; PEEP ≥ 5 cm H2O; onset time ≤ 72 h, and oxygenation index ≤ 100 [5].Exclusion criteria were as follows: complicated with malignant diseases, mental illness, drug allergies, etc.; patients aged ≤18 years or ≥75 years old; patients with liver or renal insufficiency; or patients with previous pulmonary underlying diseases.


### 2.2. Methods

Patients in the conventional treatment received mechanical ventilation, anti-infection, moderate fluid replacement, antishock, nutritional support treatment, etc. Patients in the research group received continuous HVHF on the basis of conventional treatment. The vascular access was established through the femoral vein, the replacement fluid was bicarbonate, the replacement fluid was diluted 80% before use, the flow rate of hemofiltration was 45 ml/kg/h, and heparin was used for anticoagulation. Continuous HVHF treatment was carried out for 24 hours, at least 3 days.


### 2.3. Observation Indicators

The inflammatory cytokines, lung function, serum miR-126, miR-184, MAP1-LC3 as previously reported [6], heart rate, mean arterial pressure, and blood oxygen were compared between the two groups.


### 2.4. Statistical Methods

The data in this experiment were analyzed by the SPSS21.0 software package (IBM Corp., Armonk, N.Y., USA), in which the count data were analyzed byχ2 test (n, %), and the measurement data were analyzed by t-test (mean ± SD). A two-tailed P<0.05 was determined to have statistical significance.


## 2.1. General Information

From July 1, 2015 to December 31, 2021, patients with severe ARDS caused by sepsis who were treated in our hospital were retrospectively analyzed. All patients in this study signed the informed consent form. This study was approved by the Institutional Ethical Committee of our hospital.Inclusion criteria were as follows: the clinical diagnosis was severe ARDS caused by sepsis [3]; severe hypoxia PaO2/Fi O2 ≤ 100 mm·Hg; PEEP ≥ 5 cm H2O; onset time ≤ 72 h, and oxygenation index ≤ 100 [5].Exclusion criteria were as follows: complicated with malignant diseases, mental illness, drug allergies, etc.; patients aged ≤18 years or ≥75 years old; patients with liver or renal insufficiency; or patients with previous pulmonary underlying diseases.


## 2.2. Methods

Patients in the conventional treatment received mechanical ventilation, anti-infection, moderate fluid replacement, antishock, nutritional support treatment, etc. Patients in the research group received continuous HVHF on the basis of conventional treatment. The vascular access was established through the femoral vein, the replacement fluid was bicarbonate, the replacement fluid was diluted 80% before use, the flow rate of hemofiltration was 45 ml/kg/h, and heparin was used for anticoagulation. Continuous HVHF treatment was carried out for 24 hours, at least 3 days.


## 2.3. Observation Indicators

The inflammatory cytokines, lung function, serum miR-126, miR-184, MAP1-LC3 as previously reported [6], heart rate, mean arterial pressure, and blood oxygen were compared between the two groups.


## 2.4. Statistical Methods

The data in this experiment were analyzed by the SPSS21.0 software package (IBM Corp., Armonk, N.Y., USA), in which the count data were analyzed byχ2 test (n, %), and the measurement data were analyzed by t-test (mean ± SD). A two-tailed P<0.05 was determined to have statistical significance.


## 3. Results

### 3.1. General Conditions of Enrolled Patients

There were 95 qualified patients retrieved. There was no difference in age, gender, or oxygenation index between the two groups (Table1).Table 1
General information of patients.
GenerallyStudy groupControl groupt/χ2PN5342Age58.51 ± 3.3657.96 ± 4.020.72630.470Gender0.2550.614Male2820Female2522Oxygenation index80.28 ± 4.2779.35 ± 5.140.96320.338


### 3.2. Comparison of Serum Cytokines between the Two Groups before and after Treatment

Before treatment, the levels of IL-6 (35.41 ± 5.26), IL-10 (48.62 ± 7.33), and TNF-α (9.15 ± 1.22) in the study group were comparable with the control group IL-6 (35.27 ± 5.35), IL-10 (48.37 ± 7.25), and TNF-α (9.13 ± 1.25), without significant difference (F = 3.330, 2.025, 2.551, P=0.051, 0.301, 0.210). After treatment, IL-6 (9.25 ± 1.38), IL-10 (16.29 ± 2.64), and TNF-α (3.17 ± 0.45) were significantly lower than the control group IL-6 (21.38 ± 3.42), IL-10 (34.52 ± 5.58), and TNF-α (5.58 ± 0.82). See Table 2 for details.Table 2
Serum cytokine levels in two groups of children (pg/ml,x¯±s).
GroupControl group (n = 42)Study group (n = 53)Ft/FgPt/PgIL-6Before therapy35.27 ± 5.3535.41 ± 5.263.330/8.4500.051/0.004After treatment21.38 ± 3.42^9.25 ± 1.38^∗IL-10Before therapy48.37 ± 7.2548.62 ± 7.332.025/6.1710.301/0.001After treatment34.52 ± 5.58^16.29 ± 2.64^∗TNF-αBefore therapy9.13 ± 1.259.15 ± 1.222.551/9.5510.210/0.003After treatment5.58 ± 0.82^3.17 ± 0.45^∗Note: Ft and Pt are the statistical values of time; Fg and Pg are the statistical values of factors between groups; compared with the control group,∗P<0.05; compared with before treatment, ^P<0.05.


### 3.3. Serum Levels of MiR-126, MiR-184, and MAP1-LC3 in the Two Groups

Before treatment, the miR-126 (2.06 ± 0.23), miR-184 (12.64 ± 4.17), and MAP1-LC3 (1.07 ± 0.01) of the study group were comparable with the control group of miR-126 (2.05 ± 0.06), miR-184 (12.07 ± 4.24), and MAP1-LC3 (1.05 ± 0.38), and the differences were not statistically significant (P>0.05). However, the levels of miR-126, miR-184, and MAP1-LC3 in the two groups after treatment were both significantly lower than those before the treatment, and the levels of miR-126, miR-184, and MAP1-LC3 were significantly lower in the study group than those in the control group (Table 3).Table 3
Serum levels of miR-126, miR-184, and MAP1-LC3 in the two groups.
GroupControl group (n = 42)Study group (n = 53)Ft/FgPt/PgmiR-126Before therapy2.05 ± 0.062.06 ± 0.235.08/4.140.02/0.04After treatment1.06 ± 0.13^0.94 ± 0.52^∗miR-184Before therapy12.07 ± 4.2412.64 ± 4.174.59/6.200.03/0.01After treatment5.18 ± 1.33^2.25 ± 1.61^∗MAP1-LC3Before therapy1.05 ± 0.381.07 ± 0.014.31/6.780.04/0.01After treatment0.60 ± 0.17^0.41 ± 0.12^∗Note: Ft and Pt are the statistical values of time; Fg and Pg are the statistical values of factors between groups; compared with the control group,∗P<0.05; compared with before treatment, ^P<0.05.


### 3.4. Comparison of Lung Function between the Two Groups before and after Treatment

Before treatment, the study group had comparable PEF (46.35 ± 7.29), FRC (64.88 ± 8.48), and TEF25% (42.07 ± 4.83) as the control group PEF (42.07 ± 4.83), FRC (65.27 ± 8.33), and TEF25% (41.44 ± 5.27), and there were no significant differences (P>0.05). After treatment, the PEF (67.10 ± 7.28), FRC (90.74 ± 8.63), and TEF25% (54.28 ± 5.27) of the study group were significantly higher than the control group PEF (60.17 ± 8.07), FRC (84.45 ± 9.46), and TEF25% (49.85 ± 5.12) (F = 3.54, 6.35, 6.16, P<0.05, Table 4).Table 4
Pulmonary function of the two groups of patients.
GroupControl group (n = 42)Study group (n = 53)Ft/FgPt/PgPEF (ml/s)Before therapy45.86 ± 7.9146.35 ± 7.294.12/3.540.01/0.02After treatment60.17 ± 8.07^67.10 ± 7.28^∗FRC (ml)Before therapy65.27 ± 8.3364.88 ± 8.484.37/6.350.02/0.01After treatment84.45 ± 9.46^90.74 ± 8.63^∗TEF25% (ml)Before therapy41.44 ± 5.2742.07 ± 4.834.26/6.160.03/0.01After treatment49.85 ± 5.12^54.28 ± 5.27^∗Note: Ft and Pt are the statistical values of time; Fg and Pg are the statistical values of factors between groups; compared with the control group,∗P<0.05; compared with before treatment, ^P<0.05.


### 3.5. Comparison of Heart Rate, Mean Arterial Pressure, and Blood Oxygen between Two Groups of Patients

Before treatment, the heart rate (64.10 ± 1.22), mean arterial pressure (80.15 ± 5.42), and blood oxygen (95.15 ± 2.33) of the study group were comparable with the control group heart rate (63.25 ± 1.03), mean arterial pressure (80.23 ± 2.35), and blood oxygen (94.10 ± 2.53), with no significant differences (P>0.05). After treatment, the heart rate (82.73 ± 2.54), mean arterial pressure (92.45 ± 0.27), and blood oxygen (98.10 ± 1.01) of the study group were significantly higher than the control group heart rate (65.58 ± 2.67), mean arterial pressure (81.53 ± 1.85), and blood oxygen (95.10 ± 1.20) (F = 4.91, 4.11, 5.89, P<0.05, Table 5).Table 5
Comparison of heart rate, mean arterial pressure, and blood oxygen in the two groups of patients.
GroupControl group (n = 42)Study group (n = 53)Ft/FgPt/PgHeart rate (beats/min)Before therapy63.25 ± 1.0364.10 ± 1.225.00/4.910.03/0.03After treatment65.58 ± 2.67^82.73 ± 2.54^∗Mean arterial pressure (mmHg)Before therapy80.23 ± 2.3580.15 ± 5.426.26/4.110.01/0.04After treatment81.53 ± 1.85^92.45 ± 0.27^∗Blood oxygenBefore therapy94.10 ± 2.5395.15 ± 2.334.54/5.890.03/0.02After treatment95.10 ± 1.20^98.10 ± 1.01^∗


## 3.1. General Conditions of Enrolled Patients

There were 95 qualified patients retrieved. There was no difference in age, gender, or oxygenation index between the two groups (Table1).Table 1
General information of patients.
GenerallyStudy groupControl groupt/χ2PN5342Age58.51 ± 3.3657.96 ± 4.020.72630.470Gender0.2550.614Male2820Female2522Oxygenation index80.28 ± 4.2779.35 ± 5.140.96320.338


## 3.2. Comparison of Serum Cytokines between the Two Groups before and after Treatment

Before treatment, the levels of IL-6 (35.41 ± 5.26), IL-10 (48.62 ± 7.33), and TNF-α (9.15 ± 1.22) in the study group were comparable with the control group IL-6 (35.27 ± 5.35), IL-10 (48.37 ± 7.25), and TNF-α (9.13 ± 1.25), without significant difference (F = 3.330, 2.025, 2.551, P=0.051, 0.301, 0.210). After treatment, IL-6 (9.25 ± 1.38), IL-10 (16.29 ± 2.64), and TNF-α (3.17 ± 0.45) were significantly lower than the control group IL-6 (21.38 ± 3.42), IL-10 (34.52 ± 5.58), and TNF-α (5.58 ± 0.82). See Table 2 for details.Table 2
Serum cytokine levels in two groups of children (pg/ml,x¯±s).
GroupControl group (n = 42)Study group (n = 53)Ft/FgPt/PgIL-6Before therapy35.27 ± 5.3535.41 ± 5.263.330/8.4500.051/0.004After treatment21.38 ± 3.42^9.25 ± 1.38^∗IL-10Before therapy48.37 ± 7.2548.62 ± 7.332.025/6.1710.301/0.001After treatment34.52 ± 5.58^16.29 ± 2.64^∗TNF-αBefore therapy9.13 ± 1.259.15 ± 1.222.551/9.5510.210/0.003After treatment5.58 ± 0.82^3.17 ± 0.45^∗Note: Ft and Pt are the statistical values of time; Fg and Pg are the statistical values of factors between groups; compared with the control group,∗P<0.05; compared with before treatment, ^P<0.05.


## 3.3. Serum Levels of MiR-126, MiR-184, and MAP1-LC3 in the Two Groups

Before treatment, the miR-126 (2.06 ± 0.23), miR-184 (12.64 ± 4.17), and MAP1-LC3 (1.07 ± 0.01) of the study group were comparable with the control group of miR-126 (2.05 ± 0.06), miR-184 (12.07 ± 4.24), and MAP1-LC3 (1.05 ± 0.38), and the differences were not statistically significant (P>0.05). However, the levels of miR-126, miR-184, and MAP1-LC3 in the two groups after treatment were both significantly lower than those before the treatment, and the levels of miR-126, miR-184, and MAP1-LC3 were significantly lower in the study group than those in the control group (Table 3).Table 3
Serum levels of miR-126, miR-184, and MAP1-LC3 in the two groups.
GroupControl group (n = 42)Study group (n = 53)Ft/FgPt/PgmiR-126Before therapy2.05 ± 0.062.06 ± 0.235.08/4.140.02/0.04After treatment1.06 ± 0.13^0.94 ± 0.52^∗miR-184Before therapy12.07 ± 4.2412.64 ± 4.174.59/6.200.03/0.01After treatment5.18 ± 1.33^2.25 ± 1.61^∗MAP1-LC3Before therapy1.05 ± 0.381.07 ± 0.014.31/6.780.04/0.01After treatment0.60 ± 0.17^0.41 ± 0.12^∗Note: Ft and Pt are the statistical values of time; Fg and Pg are the statistical values of factors between groups; compared with the control group,∗P<0.05; compared with before treatment, ^P<0.05.


## 3.4. Comparison of Lung Function between the Two Groups before and after Treatment

Before treatment, the study group had comparable PEF (46.35 ± 7.29), FRC (64.88 ± 8.48), and TEF25% (42.07 ± 4.83) as the control group PEF (42.07 ± 4.83), FRC (65.27 ± 8.33), and TEF25% (41.44 ± 5.27), and there were no significant differences (P>0.05). After treatment, the PEF (67.10 ± 7.28), FRC (90.74 ± 8.63), and TEF25% (54.28 ± 5.27) of the study group were significantly higher than the control group PEF (60.17 ± 8.07), FRC (84.45 ± 9.46), and TEF25% (49.85 ± 5.12) (F = 3.54, 6.35, 6.16, P<0.05, Table 4).Table 4
Pulmonary function of the two groups of patients.
GroupControl group (n = 42)Study group (n = 53)Ft/FgPt/PgPEF (ml/s)Before therapy45.86 ± 7.9146.35 ± 7.294.12/3.540.01/0.02After treatment60.17 ± 8.07^67.10 ± 7.28^∗FRC (ml)Before therapy65.27 ± 8.3364.88 ± 8.484.37/6.350.02/0.01After treatment84.45 ± 9.46^90.74 ± 8.63^∗TEF25% (ml)Before therapy41.44 ± 5.2742.07 ± 4.834.26/6.160.03/0.01After treatment49.85 ± 5.12^54.28 ± 5.27^∗Note: Ft and Pt are the statistical values of time; Fg and Pg are the statistical values of factors between groups; compared with the control group,∗P<0.05; compared with before treatment, ^P<0.05.


## 3.5. Comparison of Heart Rate, Mean Arterial Pressure, and Blood Oxygen between Two Groups of Patients

Before treatment, the heart rate (64.10 ± 1.22), mean arterial pressure (80.15 ± 5.42), and blood oxygen (95.15 ± 2.33) of the study group were comparable with the control group heart rate (63.25 ± 1.03), mean arterial pressure (80.23 ± 2.35), and blood oxygen (94.10 ± 2.53), with no significant differences (P>0.05). After treatment, the heart rate (82.73 ± 2.54), mean arterial pressure (92.45 ± 0.27), and blood oxygen (98.10 ± 1.01) of the study group were significantly higher than the control group heart rate (65.58 ± 2.67), mean arterial pressure (81.53 ± 1.85), and blood oxygen (95.10 ± 1.20) (F = 4.91, 4.11, 5.89, P<0.05, Table 5).Table 5
Comparison of heart rate, mean arterial pressure, and blood oxygen in the two groups of patients.
GroupControl group (n = 42)Study group (n = 53)Ft/FgPt/PgHeart rate (beats/min)Before therapy63.25 ± 1.0364.10 ± 1.225.00/4.910.03/0.03After treatment65.58 ± 2.67^82.73 ± 2.54^∗Mean arterial pressure (mmHg)Before therapy80.23 ± 2.3580.15 ± 5.426.26/4.110.01/0.04After treatment81.53 ± 1.85^92.45 ± 0.27^∗Blood oxygenBefore therapy94.10 ± 2.5395.15 ± 2.334.54/5.890.03/0.02After treatment95.10 ± 1.20^98.10 ± 1.01^∗


## 4. Discussion

Sepsis, an unusual systemic response to common infection or intestinal ischemia/reperfusion, may represent a pattern in the immune system’s response to injury [7]. An excessive inflammatory response is followed by a phase of immunosuppression, during which multiple organ dysfunction is present and the patient is susceptible to nosocomial infections. ARDS is a nonhydrostatic pulmonary edema and hypoxemic process associated with multiple etiologies with high morbidity and mortality (10% to 90%) characterized by increased permeability of the alveolar-capillary barrier, resulting in alveolar leukocyte infiltration and protein-rich pulmonary edema [8]. The clinical presentation was refractory hypoxemia and bilateral pulmonary infiltrates, with no evidence of left heart failure or volume overload [9]. ARDS is primarily driven by inflammatory chemokines and cytokines that are endogenously produced in response to various stimuli and events [10]. In children, one study reported a mortality rate of approximately 10% for mild and moderate ARDS and as high as 25% for severe ARDS. Inhaled oxygen (PaO2/FiO2) is closely related to mortality [11]. Hemofiltration has been proposed as a possible therapeutic option to improve oxygenation by promoting fluid removal, but its efficacy remains controversial. Several studies have concluded that continuous renal replacement therapy (CRRT), indicated for acute fluid overload (FO) and acute renal failure, improves oxygenation in patients with respiratory failure, hypoxia, and fulminant hepatitis [12–18]. However, others found no improvement in oxygenation. Even though CRRT can improve oxygenation in ARDS patients, it remains controversial whether the beneficial effects on pulmonary gas exchange are mediated by mechanisms other than fluid removal, such as through sustained removal of inflammatory mediators. miR-126, miR-184, and MAP1-LC3 have been used as markers for ARDS [6], which were employed in this study to show the efficacy of HVHF.Extracorporeal blood purification is often used to deal with poisoning. Hemofiltration removes solutes from plasma through a membrane induced by a pressure gradient [12]. HVHF is defined as continuous high-volume treatment with an ultrafiltration rate exceeding 50 mL/kg/ha per day. There are many different hypotheses about how HVHF attenuates the overexpression of systemic inflammatory mediators, restores immune homeostasis, and ultimately improves clinical outcomes. Although HVHF is frequently used for acute kidney injury, extensive experimental and some clinical evidence suggests that HVHF is effective in reducing the levels of precursors and anti-inflammatory mediators associated with systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS), which are beneficial in critically ill patients with severe inflammatory states [12]. It has the functions of expelling excess water in the human body, regulating the acid-base balance, and reducing the damage to lung tissue caused by pulmonary edema and hypercapnia; it also clears inflammatory mediators and toxin molecules and has a certain impact on the body’s immune function. HVHF also improves hemodynamics, reduces myocardial damage, and prevents the occurrence of disseminated intravascular coagulation (DIC) and immune paralysis.Continuous HVHF can meet the treatment needs of sepsis, but due to the different metabolic and infectious conditions of patients, there is no uniform rate standard. However, it is certain that it is very effective in the treatment of sepsis. In the process of HVHF, the rate of replacement fluid has a great relationship with the removal rate. Early and accurate diagnosis of ARDS would lead to a therapeutic advantage, and the findings of our study will provide valuable clues for the application of traditional Chinese medicine.In conclusion, HVHF has a good clinical effect in improving patients with severe ARDS caused by sepsis and can improve the pulmonary function of patients.



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