The Application of Dopamine Combined with Intravenous Furosemide Infusion Therapy Has an Apparent Clinical Effect in Treating Patients with Heart Failure.

Objective: To observe the efficacy and safety of dopamine plus furosemide in treating patients with heart failure.
Methods: This research included 150 patients with heart failure who were diagnosed and treated at our hospital between March 2018 and November 2020. The patients were randomly assigned to a study group or a reference group according to the data of admission (the cut-off date was June 2019). Patients in the reference group were given furosemide, whereas those in the study group were given dopamine plus furosemide intravenous pumping. Outcome measures included clinical effectiveness, heart function changes, and adverse responses.
Results: Dopamine plus furosemide resulted in higher treatment efficiency (96.00%) versus furosemide (74.67%) study group (P < 0.05). Before therapy, there was no significant change in the scores of cardiac function indices between the two groups (P > 0.05). The cardiac function of the two groups of patients was improved after treatment, and the left ventricular ejection fraction (LVEF) of the study group (44.85 ± 4.12) was higher than that of the reference group (38.45 ± 4.36), and the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVESD), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) (43.17 ± 3.98, 51.32 ± 4.25, 3045.56 ± 365.48) were lower than the reference group (47.56 ± 4.65, 56.28 ± 4.85, 4856.48 ± 395.46) (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05).
Conclusion: Dopamine plus intravenous furosemide infusion treatment has an obvious therapeutic benefit in treating patients with heart failure and dramatically enhances cardiac function without noteworthy adverse responses. It demonstrated great potential for clinical promotion.

1. Introduction

Heart failure is a condition in which the heart's pumping function is compromised for a variety of causes, and the cardiac output is insufficient to support the fundamental metabolic demands of the entire body. The blood flow in the veins fails to be completely discharged from the heart, resulting in stagnation of blood in the venous system and insufficient circulation in the arterial system [1, 2]. It mostly manifests as pulmonary congestion, hollow venous congestion, and other tissues and organs circulation congestion, such as palpitations, dyspnea, fluid retention, and lower limb edema [3].

According to statistics, in 2019, the prevalence of adult heart failure was 0.9% [4]. According to epidemiology, early symptoms of heart failure are insidious due to the compensatory mechanisms of the heart. The incidence of heart failure increases with age. The prevalence of heart failure in people over 70 years exceeds 10%, with a 5-year mortality of 50%, and the 1-year mortality rate in patients with severe heart failure can reach 50% [5, 6]. Congestion of the pulmonary circulation is the initial symptom of heart failure, which is a progressive disease requiring long-term management. Ineffective treatment will result in recurrent disease and increased patient mortality [7].

At present, heart failure is mostly manageable by comprehensive treatment, mainly including etiology treatment and symptomatic support therapy, including drugs, cardiac resynchronization therapy (CRT), and implantable cardioverter-defibrillator (ICD) [8]. Diuretics are one of the basic drugs for the treatment of heart failure [9], among which furosemide (Furosemide, Frusemide, LASIX) [10], also known as furosemide, furosemide, is a widely used treatment for congestive heart failure. It is a powerful diuretic with a strong but short effect [11]. It is primarily used to treat edema caused by heart, liver, renal, and other illnesses. However, previous experimental results revealed that diuretics may aggravate the disease condition due to renal insufficiency when used for chronic heart failure. The progression of the condition and the use of other antihypertensive medications may further impair renal function, resulting in efficacy and diuretics [12, 13]. Moreover, dopamine is the most abundant neurotransmitter in the brain, which regulates various physiological functions of the central nervous system as a neurotransmitter [14, 15]. Therefore, the use of diuretics to relieve the symptoms of patients with nephrogenic edema and cirrhosis and the addition of dopamine to stabilize the patient's cardiac function to meet the patient's therapeutic needs and enhance the efficacy are mostly recommended in clinical practice [16].

According to traditional Chinese medicine (TCM), chronic heart failure is a manifestation of heart qi deficiency, which belongs to the categories of “heart water,” “edema,” and “asthma.” The main treatment is to warm Yang and promote water. Left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) are routine clinical indicators of cardiac function. To this end, the purpose of this study is to analyze and observe the effect and safety of dopamine combined with furosemide intravenous pumping in the treatment of patients with heart failure to provide a reference for clinical treatment.

2. Subjects and Methods

2.1. Subjects of Study

This study included 150 patients with heart failure diagnosed and treated at our institution between March 2018 and November 2020, comprising 88 males and 62 females. The recruited patients were aged from 50 to 75 years. According to the random procedure, all patients were reference groups assigned to a study group or a reference group after admission. The randomization was carried out using an online web-based randomization tool (https://www.randomizer.org/). For concealment of allocation, the randomization procedure and assignment were managed by an independent research assistant who was not involved in screening or evaluation of the participants.

The cut-off point was June 2019, and 75 patients were enrolled in each group according to the principle of equal distribution. The reference group was treated with furosemide, while the study group was treated with dopamine plus furosemide.

All eligible patients provided written informed consent prior to enrollment. The study protocol was approved by the hospital ethics committee, and the ethics number was SH-HS 20180203. All procedures complied with the Declaration of Helsinki's ethical guidelines for clinical research.

2.2. Inclusion and Exclusion Criteria

Inclusion criteria: (1) patients who met the relevant diagnostic criteria in the “2014 Chinese Heart Failure Diagnosis and Treatment Guidelines” were diagnosed with heart failure by relevant imaging diagnostic tests; (2) patients who met the NYHA (New York Heart Association, United States) cardiac function classification standard; and (3) patients and their families were informed of the study and signed the consent form voluntarily.

Exclusion criteria: (1) patients with acute myocardial infarction; (2) patients with other organ failures or severe organ dysfunction; (3) patients with refractory arrhythmias; (4) patients with relevant drug allergies; (5) patients with psychiatric disorders or cognitive abnormalities that prevent normal communication; (6) patients with a severe audiovisual impairment that prevents communication; (7) patients who are pregnant or breastfeeding; and (8) patients with congenital anatomical abnormalities of the heart.

2.3. Methods

All patients were treated with conventional treatment of heart failure and drugs such as angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists.

The patients in the reference group were given furosemide alone for treatment: 20–40 mg of intravenous furosemide (national medicine approved: H31021074, Shanghai Zhaohui Pharmaceutical Co., Ltd.) was administered daily. The patients in the study group were given dopamine combined with furosemide intravenous infusion therapy as follows: 0.5–1 g/kg·min of dopamine (national medicine approved: H44022388, Guangzhou Baiyunshan Mingxing Pharmaceutical Co., Ltd.) was administered through continuous intravenous infusion, and 20–40 mg of furosemide (Chinese medicine approved: H31021074, Shanghai Zhaohui Pharmaceutical Co., Ltd.) was administered through intravenous injection, using WZ-50C2 (Zhejiang University Medical Instrument Co., Ltd.). Furthermore, adjustments to the dosage of drugs were performed according to the daily weight loss of patients or negative balance. If fluid retention is not relieved by an increase in dose, the treatment regimen was modified to 100–205 μg/min dopamine plus 10–40 mg of continuous intravenous furosemide infusion per hour.

The two groups received Zhenwu Decoction. The ingredients of the decoction included 15 g of Red ginseng, 15 g of Aconiti Lateralis Radix Praeparata, 15 g of Astragali Radix, 15 g of Poria, 12 g of Atractylodis Macrocephalae Rhizoma, 12 g of Paeoniae Radix Alba, 12 g of Alismatis Rhizoma, 10 g of Pepperweed Seed, 10 g of ginger, 10 g of cinnamon, and 10 g of dried Aconiti Lateralis Radix Praeparata. The above herbs were decocted with 1200 mL of water to obtain 500 mL of filtrate and administered with a half dose in the morning and a half in the evening. The treatment was discontinued after 30 days of treatment or patient death.

2.4. Outcomes

Clinical efficacy: The treatment effect was evaluated according to the clinical symptoms and was divided into markedly effective, effective, and ineffective. Markedly effective: all the clinical symptoms disappeared after treatment. Effective: clinical symptoms were alleviated after treatment. Ineffective: the clinical symptoms were not improved. The total effective rate of the two groups was calculated and compared. Total response rate = (significant + effective)/total number of cases × 100%.

Cardiac function: Routine examination by echocardiography was used to measure the cardiac function-related indicators in the two groups before and after treatment, including left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP).

Adverse reactions: The occurrence of adverse reactions in all patients was recorded, including nausea, headache, hypokalemia, and blurred vision, and the incidence of adverse reactions in the two groups was calculated and compared between groups.

2.5. Data Analysis

SPSS22.0 software was used for data analysis. Normally distributed measurement data were expressed as mean plus or minus standard deviation (n=((2(μ+μ)2p(1 − p))/δ2)). The comparison of means between two groups was preceded by the chi-squared F-test. Data with chi-squared differences was tested with the independent samples t-test, and data with nonchi-squared differences were tested with the independent samples t-test. Intragroup pre-post comparisons were performed with paired samples t-test. The counting data was represented by the number of cases (%) and tested by chi-square test. P < 0.05 indicated that the comparison was statistically significant.

3. Results

3.1. Ba Characteristics

75 patients were enrolled in the reference group, including 42 males and 33 females, aged 52–72 (62.85 ± 6.18) years, disease course of 3–6 (4.17 ± 1.32) years, 35 cases of coronary heart disease, 23 cases of hypertensive heart disease, 10 cases of dilated cardiomyopathy, 5 cases of cardiomyopathy, and 2 cases of congenital heart disease. The study group included 75 patients, including 46 males and 29 females, aged 50–75 (62.33 ± 6.25) years, disease course of 2–6 (4.25 ± 1.41) years, 32 cases of coronary heart disease, 24 cases of hypertensive heart disease, 9 cases of dilated cardiomyopathy, 6 cases of cardiomyopathy, and 4 cases of congenital heart disease. The patient characteristics of the two groups were comparable (P > 0.05) (Table 1).

Table 1

Comparison of general data of the two groups of patients .

Group	Number of cases	Gender		Age (years)		Duration of disease (years)		Type of disease
		Male	Female	Scope	Average	Scope	Average	Coronary heart disease	Hypertensive heart disease	Dilated cardiomyopathy	Cardiac disease	Congenital heart disease
Reference group	75	42	33	52–72	62.85 ± 6.18	3–6	4.17 ± 1.32	35	23	10	5	2
Study group	75	46	29	50–75	62.33 ± 6.25	2–6	4.25 ± 1.41	32	24	9	6	4
t	—	—	—	—	0.512	—	0.359	—	—	—	—	—
P	—	—	—	—	0.609	—	0.720	—	—	—	—	—

3.2. Clinical Effectiveness

There were 23 (30.67%) cases of markedly effective, 33 (44.00%) cases of effective, and 19 (25.33%) cases of ineffective in the reference group. There were 33 cases of markedly effective, 39 (52.00%) cases of effective, and 3 (4.00%) cases of ineffective in the study group. The study group showed higher treatment efficacy (96.00%) than the references group (74.67%) (Table 2).

Table 2

Comparison of clinical efficacy between the two groups of patients (%).

Group	Number of cases	Markedly effective	Effective	Ineffective	Total efficiency
Reference group	75	23 (30.67)	33 (44.00)	19 (25.33)	56 (74.67)
Study group	75	33 (44.00)	39 (52.00)	3 (4.00)	72 (96.00)
x 2	—	13.636
P	—	<0.001

3.3. Cardiac Function Index Scores

The results showed no significant difference in cardiac function index scores between the two groups before treatment (P > 0.05). The cardiac function of the two groups of patients was improved after treatment, and the LVEF of the study group (44.85 ± 4.12) was higher than that of the reference group (38.45 ± 4.36). (44.85 ± 4.12). Higher than the reference group (38.45 ± 4.36), LVESD, LVEDD, NT-proBNP (43.17 ± 3.98, 51.32 ± 4.25, 3045.56 ± 365.48) were lower than the reference group (47.56 ± 4.65, 56.28 ± 4.85, 4856.48 ± 395.46) (P < 0.05) (Table 3).

Table 3

Comparison of cardiac function scores between the two groups before and after treatment.

Group	Time	Reference group (n = 75)	Study group (n = 75)	t	P
LVEF (%)	Before therapy	32.14 ± 4.24	31.99 ± 4.53	0.209	0.835
	After treatment	38.45 ± 4.36∗	44.85 ± 4.12∗	9.240	<0.001
LVESD (mm)	Before therapy	51.29 ± 3.48	51.32 ± 3.68	0.051	0.959
	After treatment	47.56 ± 4.65∗	43.17 ± 3.98∗	6.211	<0.001
LVEDD (mm)	Before therapy	61.02 ± 5.12	60.98 ± 4.97	0.049	0.961
	After treatment	56.28 ± 4.85∗	51.32 ± 4.25∗	6.661	<0.001
NT-proBNP (ng/L)	Before therapy	7568.15 ± 590.15	7572.45 ± 591.56	0.045	0.964
	After treatment	4856.48 ± 395.46∗	3045.56 ± 365.48∗	29.124	<0.001

Note: indicates that the difference between before and after treatment in the same group is statistically significant, P < 0.05.

3.4. Adverse Reaction

There were 2 (2.67%) cases of nausea, 4 (5.33%) cases of headache, 1 (1.33%) case of hypokalemia, and 2 (2.67%) cases of blurred vision in the reference group. There were 2 (2.67%) cases of nausea, 4 (5.33%) cases of headache, 1 (1.33%) case of hypokalemia, and 2 (2.67%) cases of blurred vision in the study group. There was no statistically significant difference in the incidence of adverse events between the two groups (P > 0.05) (Table 4).

Table 4

Comparison of adverse events in the two groups of patients (%).

Group	Number of cases	Nausea	Headaches	Hypokalemia	Blurred vision	Total incidences
Reference group	75	2 (2.67)	4 (5.33)	1 (1.33)	1 (1.33)	8 (10.67)
Study group	75	2 (2.67)	4 (5.33)	1 (1.33)	2 (2.67)	9 (12.00)
x 2	—	0.066
P	—	0.797

4. Discussion

Heart failure is a syndrome of pulmonary or body circulation stasis caused by the fatigue and low blood expulsion of the heart in the process of venous return, and the amount of blood expulsion is not compatible with the metabolic needs of the body's organs and tissues, resulting in fluid retention, which is one of the important factors in the aggravation of heart failure disease. Therefore, a scientific approach to clinical improvement is required to avoid the deterioration of heart failure disease in patients [17]. Clinically, diuresis is the mainstay of conventional therapy for patients with heart failure, and diuretics are critical for treating patients with heart failure. The most critical symptom of heart failure is fluid retention, which induces pulmonary congestion and peripheral edema, as well as shortness of breath and exhaustion, and restricts exercise tolerance. Diuretics inhibit the reabsorption of sodium or chloride in certain parts of the renal tract, inhibit sodium retention in heart failure, and reduce venous recovery and preload, thereby mitigating pulmonary congestion and improving exercise tolerance. Furosemide is a representative of loop diuretics; its scientific name is 4-Chloro-2-[(furan-2-ylmethyl) amino]-5-sulfamoylbenzoic acid [18]. It is primarily used for the treatment of edema, hypertension, acute pulmonary edema, and cerebral edema. It effectively enhances urinary sodium excretion and improves free water clearance and renal function in terms of fluid retention. However, as the condition advances, reduced renal blood flow or electrolyte balance, intestinal edema, or small bowel hypoperfusion impede drug delivery, resulting in diuretics' failure to establish diuretic resistance in the absence of a response.

According to current guidelines, low doses of dopamine (scientific name; DA, or 3,4-dihydroxyphenylalanine (DOPA)) may be considered to overcome diuretic resistance [19]. It is a neurotransmitter and is an endogenous nitrogen organic compound. Tyrosine dihydroxy hitches in the metabolic process of phenylalanine intermediate [20], a chemical that helps cells carry impulses, brain secretion, and people's desires and feelings. It also conveys information about excitement and happiness [21]. Accordingly, this study recruited 150 patients with heart failure diagnosed and treated in our hospital from March 2018 to November 2020 for analysis. In TCM, heart failure belongs to the category of “palpitation,” and the main pathogenesis is Yang deficiency [22]. The heart is the host of blood vessels, the kidneys store essence, and the kidney vessels are superiorly connected to the heart. The patient's Yang deficiency causes deficiency of Yang in the heart and kidney, resulting in blood stasis in the veins and collaterals and causing disease onset. For patients with heart and kidney yang deficiency type of heart failure, the main treatment principle is to benefit qi and warm yang, invigorate blood, and promote water circulation. Zhenwu Decoction has a targeted effect for conditions such as internal stagnation of water and qi and deficiency of spleen and kidney yang.

The results showed that the total clinical efficiency (96.00%) of the patients in the study group was significantly higher than that in the reference group (74.67%). Before the clinical manifestations of diuretic resistance, the combination of dopamine and furosemide could stimulate dopamine receptors, dilate kidneys, mesentery, and coronary arteries, increased renal blood flow. All this will fully optimize the action of diuretics, reduce fluid retention, maintain proper blood pressure levels during venous pumping, and have mild positive inotropic effects and changes in heart rate. It has a modest effect, total peripheral resistance is reduced, and symptoms and signs can be greatly improved. The combination of the two effectively improves glomerular filtration and renal vascular circulation and raises the patient's urine excretion and salt excretion. Based on the findings, it is obvious that the use of dopamine plus furosemide intravenous infusion in the treatment of patients with heart failure can dramatically improve symptoms. The effect is significant and consistent with the research results of Zhanting et al. The results of this study also showed that the cardiac function of the two groups of patients improved after treatment. The LVEF level of patients in the study group was higher than in the reference group. LVESD, LVEDD, and NT-probNP were lower than the reference group. Dopamine is a key neurotransmitter that improves people's mood and condition and increases the overall contractility of the myocardium, increases cardiac blood production, selectively dilates renal blood vessels, accelerates renal blood flow and blood circulation, reduces the oxygen consumption of the myocardium, and enhances the urine volume and frequency of patients. It is mainly used for the treatment of renal failure, heart disease and heart failure, and may significantly increase the cardiac output of patients. The combination of the two has a greater impact and assists to mitigate high cardiac load in patients and enhances cardiac function. Furthermore, for intravenous infusion, this study used a micropump, which lowers blood pressure and avoids renal insufficiency. Furthermore, controlled drug concentrations allow for a more concentrated effect. There was no significant difference in the overall incidence of adverse reactions between the two groups, suggesting that intravenous pumping of dopamine combined with furosemide is not associated with an increased risk of adverse reactions and yields a manageable safety.

Zhenwu Decoction warms the spleen and kidney, facilitates urination, and dispels water evils [24]. In the formula, Aconiti Lateralis Radix Praeparata moves moisture and transforms qi, helps Yang to warm the kidneys and spleen, Atractylodis Macrocephalae Rhizoma dries dampness and strengthens the spleen, Poria permeates dampness and facilitates drainage, ginger, and Paeoniae Radix Alba expels dampness, strengthens the spleen, and warms the middle. Paeoniae Radix Alba promotes diuresis and invigorates the blood vessels, and Aconiti Lateralis Radix Praeparata is excessively hot and depletes yin qi [24, 25]. Astragali Radix tonifies water and dampness and nourishes the middle energy, Red ginseng greatly tonifies the vital energy, cinnamon, and Aconiti Lateralis Radix Praeparata tonifies the heart and kidney yang energy, Alismatis Rhizoma and Pepperweed Seed tonify water and reduce swelling [26]. The limitations of this study are the small sample size and the absence of long-term follow-up. Future studies will be conducted with a larger sample size and long-term follow-up to obtain more reliable data.

In conclusion, dopamine plus intravenous furosemide infusion treatment has an obvious therapeutic benefit in treating patients with heart failure and dramatically enhances cardiac function without noteworthy adverse responses. It demonstrated great potential for clinical promotion.