Clinical Study on the Retention Enema with Modified Dahuang Mudan Decoction in Treating Lower-Jiao Obstruction Syndrome Caused by Severe Pneumonia Complicated with Heart Failure

Yaonan DU, Peilin ZHAO, Bo LI, Jing TIAN, Shihong XU*, Zhongxin PU

1. Department of Cardiology, Nanchong Chinese Medicine Hospital Affiliated to North Sichuan Medical College, Nanchong 637000, China; 2. Department of Acute Injury Diseases, Nanchong Chinese Medicine Hospital Affiliated to North Sichuan Medical College, Nanchong 637000, China; 3. Department of Critical Medicine, Nanchong Chinese Medicine Hospital Affiliated to North Sichuan Medical College, Nanchong 637000, China

Abstract [Objectives] To treat patients with Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure using the retention enema with Modified Dahuang Mudan Decoction, and to observe the effect and safety of this treatment on inflammatory indicators, cardiac function, gastrointestinal function and multiple organ failure in patients with Lower-Jiao (lower energizer) Obstruction Syndrome caused by severe pneumonia complicated with heart failure. [Methods] 54 patients with Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure diagnosed in Nanchong Chinese Medicine Hospital from January 2020 to December 2021 were randomly divided into experimental group (n=27) and control group (n=27). The control group was given conventional treatment combined with 0.9% sodium chloride injection (100 mL)+glycerine enema (40 mL). The treatment group was treated with Modified Dahuang Mudan Decoction on the basis of conventional treatment for 7 d. The efficacy indicators and adverse events such as white blood count (WBC), C-reactive protein (CRP), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), Lausanne Intestinal Failure Estimation (LIFE) and multiple organ dysfunction score (MODS) were observed. [Results] (i) There was no significant difference in WBC, PCT, CRP and NT-proBNP between the two groups before treatment. All indicators after treatment were significantly lower than those before treatment in both groups (P<0.05). The levels of WBC, PCT and CRP in the treatment group were lower than those in the control group after treatment (P<0.05), and there was no significant difference in NT-proBNP between the two groups after treatment (P>0.05), but the difference in NT-proBNP before and after treatment in the treatment group was higher than that in the control group. (ii) The LIFE of the two groups decreased significantly after treatment, and the improvement of LIFE of the treatment group was better than that of the control group (P<0.05). (iii) The MODS of the two groups decreased significantly after treatment (P<0.05), and the degree of decrease after treatment in the treatment group was higher than that in the control group (P<0.05). (iv) There was no significant difference in all-cause mortality between the two groups (P>0.05). (v) No serious adverse events were found in both groups during the treatment period. [Conclusions] The conventional treatment, combined with the retention enema with Modified Dahuang Mudan Decoction could further reduce the inflammatory indicators, improve cardiac function, improve intestinal function and organ function, and the safety was good.

Key words Modified Dahuang Mudan Decoction, Retention enema, Severe pneumonia complicated with heart failure, Lower-Jiao (lower energizer) Obstruction Syndrome

1 Introduction

Severe pneumonia is a common critical disease with rapid progress, high mortality and other characteristics, and it poses a serious threat to people’s life and health[1-2]. Heart failure is the most common complication of severe pneumonia[3]. In patients with acute exacerbation of heart failure, blood stasis in the lungs induces or aggravates pneumonia, and even leads to severe pneumonia[4]. The two influence each other closely, and in serious cases, it can lead to multiple organ failure, sepsis, septic shock, respiratory distress syndrome and other critical cases, directly affecting the quality of life of patients, threatening the life of patients[3].

Gastrointestinal dysfunction is a common complication of severe patients with severe pneumonia complicated with heart failure, and it can aggravate the condition and affect the prognosis[5-6]. Gastrointestinal dysfunction falls into the category of Lower-Jiao (lower energizer) Obstruction Syndrome in traditional Chinese medicine[7]. Severe pneumonia and heart failure are closely related to the dysfunction of Tri-Jiao (triple energizers)[7-8]. In patients with severe pneumonia complicated with heart failure, there is disturbance of visceral function, the fluid transportation and transformation breaks down, the function of small intestinal secretion is abnormal, and the intestinal conduction function is disordered, which leads to the Lower-Jiao Obstruction Syndrome, such as oliguria, abdominal distension, and constipation. At the same time, the Lower-Jiao obstruction and visceral qi obstruction will aggravate the blockage of lung qi and the disorder of systemic functional activities of qi, thus aggravating the disease[9]. The study found that clearing the hollow viscera and removing blood stasis is an effective measure for the treatment of gastrointestinal dysfunction in severe patients (Lower-Jiao Obstruction Syndrome)[10]. The retention enema with traditional Chinese medicine can avoid the first-pass effect of liver, prevent the destructive effect of gastric acid and digestive enzymes on drugs, reduce the stimulation of drugs on gastric mucosa, and show quick effect, which is especially suitable for critically ill patients[11]. In this study, 54 patients were enrolled in a randomized controlled trial (RCT) to evaluate the efficacy and safety of the retention enema with Modified Dahuang Mudan Decoction in the treatment of Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure. The results are reported as follows.

2 Data and methods

2.1 Diagnostic criteria of Western medicine(i) The diagnostic criteria of severe pneumonia put forward by the American Association of Infectious Diseases/American Thoracic Society, that is, the main criteria: invasive mechanical ventilation is required, and septic shock needs vasoconstrictor treatment; secondary criteria: respiratory rate≥30/min, oxygenation indicators≤250, hypothermia (<36.0 ℃), disturbance of consciousness/orientation, azotemia (urea nitrogen≥20 mg/dL), leukopenia (<4.0×109/L), low platelet count (<10×109/L), multiple lobar infiltration, hypotension, need of strong fluid resuscitation. Those who meet 1 item of major criteria or more than 3 items of secondary criteria can be diagnosed as severe pneumonia[12]. (ii) Diagnostic criteria of heart failure: refer to theChineseGuidelinefortheDiagnosisandTreatmentofHeartFailure2018, history of coronary heart disease, hypertension, risk factors of heart failure, use of diuretics, dyspnea,etc.; signs: lung rale, edema of both lower extremities, heart murmur, jugular vein filling, apical pulsation lateral shift or diffusion; auxiliary examination: abnormal electrocardiogram; chest X-ray indicates pulmonary congestion, pulmonary edema and cardiac enlargement; NT-proBNP≥125 ng/L; ultrasonic cardiogram indicates abnormal cardiac structure and/or function. If the patients meet either of the first two items, plus the third item, it is judged as heart failure[13].

2.2 Diagnostic criteria of TCM syndromesDiagnostic criteria of Lower-Jiao Obstruction Syndrome. Symptoms and signs: abdominal distension, constipation; short voidings of scant urine; tongue vein: dark red or purple dark tongue, yellow thick or greasy fur, tight or strong or slippery pulse; it can be diagnosed if patients have any one of the symptoms combined with the tongue and pulse.

2.3 Inclusion criteria40 years≤age≤89 years; meeting the diagnostic criteria of severe pneumonia and heart failure; TCM syndrome differentiation of phlegm-heat; the subjects are informed and voluntarily sign the informed consent form.

2.4 Exclusion criteriaRespiratory depression or respiratory and cardiac arrest; malignant arrhythmia and acute myocardial infarction; accompanied by malignant tumor or tuberculosis; severe liver and kidney damage (glutamic pyruvic transaminase in liver function>3 times ULN (upper limit of normal value), serum creatinine>2 times ULN (upper limit of normal value); severe endocrine diseases, autoimmune diseases, inflammatory or malabsorption bowel diseases; abnormal blood coagulation and bleeding tendency; participate in other researchers in recent 2 months.

2.5 Generation and concealment of randomized planRCT was adopted in this study, and SPSS 19.0 statistical software was used to generate random number table. Balanced grouping was used and the random serial number was kept by special personnel. The trained clinician acted as the case collector, determined the subjects who met the selection criteria and reported to the serial number custodian by telephone. The custodian issued a random serial number to determine the case grouping and the corresponding treatment plan.

2.6 General informationFrom January 2020 to December 2021, 54 patients with severe pneumonia complicated with phlegm-heat syndrome in Nanchong Chinese Medicine Hospital were randomly divided into experimental group (n=27) and control group (n=27). There was no significant difference in age and sex between the two groups (P>0.05, Table 1).

Table 1 Comparison of basic data between the experimental group and the control group before grouping

2.7 Treatment methodsThe subjects in both groups were given conventional treatments such as anti-infection, expectorant, spasmolysis and asthma, nutritional support, oxygen inhalation, mechanical ventilation, loop diuretics, vasoactive drugs, and positive inotropic drugs. Different antibiotics were selected according to the sensitivity of patients to drugs and the results of pathogenic microorganisms. The control group was given conventional treatment combined with 0.9% sodium chloride injection (100 mL)+glycerine enema (40 mL). On the basis of conventional treatment, the treatment group was given 140 mL of Modified Dahuang Mudan Decoction (raw rhubarb 15 g, peony bark 15 g, mirabilite 10 g, wax gourd seed 10 g, bark of magnolia 15 g, citron fruit 15 g, rooted salvia 15 g, red peony 15 g, oriental wormwood 10 g, gardenia 10 g) for retention enema (the enema solution was heated to 38 ℃ in a thermostat).

2.8 Observation indicatorsWhite blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), N-terminal pro-brain natriuretic peptide (NT-proBNP), Lausanne Intestinal Failure Estimation (LIFE) and multiple organ dysfunction score (MODS) were observed before treatment and 8 d after treatment; the incidence of adverse events and other safety indicators were observed.

2.9 Statistical methodsSPSS 19.0 statistical analysis software was used for statistical analysis. The measurement data were statistically described by mean±standard deviation (x±S) and statistically analyzed by two independent samplet-test. If the data did not conform to the normal distribution or/and the variance was uneven, the median and quartile were used for statistical description, and the Wilcoxon rank sum test was used for statistical analysis. The counting data were described by frequency and compared byx2test.

3 Results and analysis

3.1 Comparison of WBC, CRP, PCT and NT-proBNP before and after treatmentTable 2 showed that there was no significant difference in WBC, PCT, CRP and NT-proBNP between groups before treatment (P>0.05). The indicators after treatment were significantly lower than those before treatment in both groups (P<0.05). The levels of WBC, PCT and CRP in the treatment group were lower than those in the control group after treatment (P<0.05). There was no significant difference in NT-proBNP between the two groups after treatment (P>0.05), but the difference in NT-proBNP before and after treatment in the treatment group was higher than that in the control group (P<0.05).

Table 2 Comparison of WBC, CRP, PCT and NT-proBNP between experimental group and control group before and after treatment

3.2 Comparison of LIFE before and after treatmentTable 3 showed that there was no significant difference between the two groups before treatment (P>0.05); the score after treatment in both groups was significantly lower than that before treatment (P<0.05), and the score in the treatment group was lower than that in the control group (P<0.05).

Table 3 Comparison of LIFE between the experimental group and the control group before and after treatment

3.3 Comparison of MODS before and after treatmentTable 4 showed that there was no significant difference between the two groups before treatment (P>0.05); the score after treatment was significantly lower than that before treatment in both groups (P<0.05), and the score in the treatment group was significantly lower than that in the control group (P<0.05).

Table 4 Comparison of TCM syndrome score between the experimental group and the control group before and after treatment

3.4 Comparison of all-cause mortalityThe all-cause mortality rates of the experimental group and the control group were 7.4% and 3.7%, respectively. There was no significant difference in all-cause mortality between the two groups (P>0.05).

3.5 Comparison of safety indicatorsNo serious adverse events were found in both groups during the treatment period.

4 Discussion

In this study, patients with Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure were selected as the object of study. A randomized and control study was used to evaluate the effect and safety of this treatment on inflammatory indicators, NT-proBNP, gastrointestinal function and multiple organ failure in patients with Lower-Jiao Obstruction Syndrome caused by severe pneumonia complicated with heart failure. WBC, CRP, PCT and NT-proBNP played an important role in evaluating the severity and prognosis of severe pneumonia complicated with heart failure, while LIFE and MODS played an important role in evaluating the prognosis of critically ill patients with gastrointestinal dysfunction. The results showed that compared with conventional treatment, the retention enema with Modified Dahuang Mudan Decoction could further reduce the inflammatory indicators, improve cardiac function, improve intestinal function and organ function, and be beneficial to the recovery and prognosis of patients and there were no obvious adverse events in the course of treatment. This showed that the retention enema with Modified Dahuang Mudan Decoction in the treatment of severe pneumonia complicated with heart failure was safe and effective, which was better than conventional treatment.

According to modern medicine, gastrointestinal dysfunction is a common complication for severe patients with severe pneumonia complicated with heart failure, and gastrointestinal dysfunction can lead to the translocation of bacteria and endotoxin and the release of inflammatory mediators and cytokines, thus triggering systemic inflammatory response syndrome (SIRS), which can eventually lead to systemic multiple organ dysfunction syndrome (MODS) or death[14]. Gastrointestinal dysfunction falls into the category of Lower-Jiao Obstruction Syndrome in traditional Chinese medicine. The "Tri-Jiao" of traditional Chinese medicine is the pathway of vital energy and water fluid movement. In severe pneumonia, turbid phlegm accumulated in the lung obstructs the airway, causes lung-energy disorder, and the main clinical manifestation of heart failure is abnormal metabolism of body fluid. It can be seen that severe pneumonia and heart failure are closely related to the dysfunction of Tri-Jiao. In patients with severe pneumonia complicated with heart failure, there is disturbance of visceral function, the fluid transportation and transformation breaks down, the function of small intestinal secretion is abnormal, and the intestinal conduction function is disordered, which leads to the Lower-Jiao Obstruction Syndrome, such as oliguria, abdominal distension, and constipation. At the same time, the Lower-Jiao obstruction and visceral qi obstruction will aggravate the blockage of lung qi and the disorder of systemic functional activities of qi, thus aggravating the disease. Therefore, timely and effective treatment of Lower-Jiao Obstruction Syndrome is conducive to the remission and rehabilitation of the disease. The six hollow viscera must keep its unobstructed. The basic pathogenesis of Lower-Jiao Obstruction Syndrome is the disorder of the stomach qi and the blockage of fu-qi, and the blood stasis runs through heart failure all the time[15], so it is mainly treated by regulating the function of the stomach and promoting the circulation of qi combined with promoting blood circulation, removing blood stasis and selecting the retention enema with Modified Dahuang Mudan Decoction.

Severe pneumonia complicated with heart failure is a common critical illness in cardiovascular medicine, respiratory and critical care departments, with rapid progress and high mortality[1]. Lower-Jiao Obstruction Syndrome is also a common TCM syndrome type of cardiopulmonary critically ill patients[7-8]. Gastrointestinal dysfunction is its main clinical manifestation. Lower-Jiao Obstruction Syndrome and gastrointestinal dysfunction affect the condition and prognosis of critically ill patients, and need timely and effective intervention, but it is often ignored. At present, there are few reported clinical studies on the combination of traditional Chinese and Western medicine in the treatment of severe pneumonia complicated with heart failure, and there is also a lack of clinical research on the combination of traditional Chinese and Western medicine in the treatment of Lower-Jiao Obstruction Syndrome. The gastrointestinal tract is the largest storage of bacteria in the whole body, and it is also the trigger of SIRS, playing a very important role in the treatment and prognosis of critically ill patients. Traditional Chinese medicine has obvious advantages in the treatment of Lower-Jiao Obstruction Syndrome or gastrointestinal dysfunction. Therefore, this research project is carried out to actively explore the integrated traditional Chinese and Western medicine in the treatment of severe pneumonia with heart failure.