Clinical effects of dexmedetomidine on patients with sepsis and myocardial injury

Abstract

This study aimed to explore the organ-protective effects of dexmedetomidine in patients with sepsis combined with myocardial injury. From December 2021 to December 2023, 263 sepsis patients with myocardial injury were included based on inclusion and exclusion criteria. They were divided into an experimental group (n = 122), who had previously received dexmedetomidine, and a control group (n = 141), who had received midazolam. After matching baseline characteristics, the treatment outcomes between the 2 groups were compared. In a propensity score-matched cohort of 263 patients, each group had 62 individuals with balanced baseline characteristics. The experimental group showed significantly lower heart rates on days 1, 3, and 7 compared to the control (P < .05). Biomarkers high-sensitivity troponin I and creatine kinase-MB decreased significantly by days 3 and 7, with lower levels in the experimental group. B-type natriuretic peptide levels were also lower in the experimental group on days 3 and 7. Heart function improved in both groups, with the experimental group showing better outcomes. Inflammatory markers decreased significantly after 7 days, with the experimental group having lower levels. Hospitalization duration was similar between groups. Dexmedetomidine reduces heart rate and inflammatory markers, protects myocardial cells, and improves cardiac function in patients with sepsis and myocardial injury. It shows potential as a treatment option, with future research needed to assess its long-term efficacy and safety.

1. Introduction

Sepsis is a systemic inflammatory response syndrome triggered by infection, with an extremely high mortality rate. According to incomplete statistics, approximately 17.5 million people worldwide are affected by this condition each year, with a mortality rate ranging from 30% to 70%, and it is highly contagious. Sepsis often leads to multiple organ dysfunction, with the heart being one of the most commonly affected organs, and around 50% of patients experiencing myocardial injury.^[1–3] Myocardial injury results from complex inflammatory responses and a “cytokine storm,” which cause ischemic and hypoxic damage to myocardial cells, significantly increasing patient mortality. During clinical management of sepsis with myocardial injury, various invasive procedures often cause discomfort and pain, potentially exacerbating the condition. Thus, appropriate sedative treatment is crucial.^[4] However, traditional analgesic and sedative methods often fail to effectively reduce organ metabolic oxygen consumption, which is vital for recovery in critically ill patients.

Recent studies have found that dexmedetomidine, while providing excellent sedation and analgesia, also exhibits significant cardioprotective effects. Dexmedetomidine is a selective α2-adrenergic receptor agonist with pronounced sedative, analgesic, and anxiolytic effects, without affecting respiration. It can modulate sympathetic nervous system tone, improve neuroendocrine stress responses, reduce metabolic disturbances, and thereby enhance organ metabolic status and overall therapeutic outcomes.^[5] However, research on the use of dexmedetomidine in patients with sepsis and myocardial injury is relatively sparse, with most studies focusing on its application during cardiovascular surgery.^[6]

Therefore, this study aims to investigate the organ-protective effects of dexmedetomidine in patients with sepsis and myocardial injury and compare it with midazolam. Although midazolam is a commonly used sedative in clinical practice, its drug label and relevant literature do not indicate any myocardial protective effects. By comparing dexmedetomidine with midazolam, this study seeks to eliminate potential confounding factors related to the sedative effects of dexmedetomidine, thus providing a strong basis for selecting an appropriate sedative drug. The results of this study are expected to offer important references for sedative treatment in patients with sepsis and myocardial injury in future clinical practice.

2. Materials and methods

2.1. Study design

This study was approved by the Ethics Committee of The First College of Clinical Medical Science. This study is a retrospective analysis that included patients with sepsis and myocardial injury from our hospital between December 2021 and December 2023. A total of 263 patients were enrolled based on the inclusion and exclusion criteria. The patients were divided into 2 groups according to their previous treatment with either dexmedetomidine or midazolam: the experimental group (n = 122) and the control group (n = 141). The experimental group had previously received dexmedetomidine treatment, while the control group had received midazolam. After matching the baseline information of both groups, we compared the effects of relevant treatment indicators.

2.1.1. Inclusion criteria

Diagnosis of sepsis combined with myocardial injury: sepsis was diagnosed according to the criteria established by the 2008 International Sepsis Conference in Washington, USA. Myocardial injury was defined as high-sensitivity troponin I (hs-TnI) ≥ the upper limit of normal (0.1 µg/L). Age ≥ 18 years. Previous treatment with either standard treatment or dexmedetomidine, meeting the standards of the treatment methods described subsequently.

2.1.2. Exclusion criteria

Pregnant women. History of long-term corticosteroid use. Long-term use of sedatives. History of preexisting cardiac diseases, such as severe valvular heart disease or coronary artery syndrome. Immune deficiency diseases. Hematological disorders. Cancer patients undergoing chemotherapy. Patients with psychiatric disorders.

2.2. Treatment methods

2.2.1. Standard treatment

Upon admission, all patients received empirical antibiotic therapy within 1 hour. Standard treatment measures included fluid resuscitation, organ function protection, maintenance of electrolyte and acid–base balance, adjustment of nutritional metabolism, and mechanical ventilation with endotracheal intubation if necessary. For patients on mechanical ventilation, continuous or intermittent analgesia with sufentanil was administered to achieve a Behavioral Pain Scale score of <6.

2.2.2. Control group treatment

Patients in the midazolam group received midazolam in addition to standard treatment. The dosing regimen was 0.1 mg/kg administered slowly via intravenous push over 30 seconds, followed by continuous infusion via a microinfusion pump at a rate of 0.03 to 0.15 mg/kg/h. However, midazolam has limitations. While it is effective in providing sedation, it lacks cardioprotective and anti-inflammatory properties, which are increasingly recognized as important in managing sepsis and myocardial injury. Furthermore, midazolam can induce respiratory depression, which may complicate care in critically ill patients, especially those on mechanical ventilation.

2.2.3. Experimental group treatment

Patients in the dexmedetomidine group received dexmedetomidine in addition to standard treatment. The dosing regimen was an initial bolus of 1 µg/kg administered slowly via intravenous push over 10 minutes, followed by continuous infusion via a microinfusion pump at a rate of 0.2 to 0.7 µg/kg/h.

Both groups aimed to maintain Ramsay sedation scores between 3 and 4 as the ideal sedation standard. The Ramsay Sedation Scale is as follows: 1: patient is anxious, agitated, or restless. 2: patient is awake, calm, and cooperative. 3: patient is drowsy but responds promptly to verbal commands. 4: patient is in a light sleep state but can be quickly awakened. 5: patient is asleep and responds only to physical stimulation. 6: patient is deeply asleep and does not respond to any stimuli.

2.3. Propensity score matching

To eliminate the impact of confounding factors, we employed propensity score matching to adjust for baseline factors that could influence differences in treatment outcomes between the 2 groups. Based on a review of the literature, the following confounding factors were matched: age, gender, site of infection, Sequential Organ Failure Assessment (SOFA) score, Acute Physiology and Chronic Health Evaluation II (APACHE II) score, duration of sedation, mode of mechanical ventilation, heart rate (HR), myocardial enzyme levels (MYO), hs-TnI, creatine kinase-MB (CK-MB), B-type natriuretic peptide (BNP), left ventricular ejection fraction (LVEF), left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVEDD), procalcitonin (PCT), interleukins (IL-1β, IL-6, IL-8), and tumor necrosis factor-alpha (TNF-α), as well as history of diabetes and hypertension. Subsequent comparison of outcomes was conducted with these variables uniquely adjusted between the 2 groups.

2.4. Outcome measures

1. SOFA score: this score assesses organ function in critically ill patients across 6 systems: respiratory, coagulation, hepatic, cardiovascular, central nervous, and renal. Each system is scored from 0 to 4, with higher scores indicating worse organ function.

2. APACHE II score: APACHE II evaluates the severity of illness in ICU patients. It consists of 2 parts: Acute Physiology Score: based on physiological parameters at ICU admission (e.g., temperature, heart rate, respiratory rate, blood pressure, arterial oxygen partial pressure), with scores ranging from 0 to 71. Chronic Health Score: considers the patient’s chronic health status before ICU admission (e.g., presence of chronic diseases), scored as 0 or 1.

3. HR: measured using a color Doppler ultrasound diagnostic device.

4. Myocardial injury markers: peripheral blood samples are collected to determine hs-TnI and CK-MB.

5. Heart failure indicators: peripheral blood samples are collected to measure BNP. Heart function indicators are measured using color Doppler ultrasound: LVEF: measures the percentage of blood pumped out of the left ventricle with each heartbeat. LVESD: measures the diameter of the left ventricle at the end of systole. LVEDD: measures the diameter of the left ventricle at the end of diastole.

6. Inflammatory markers: peripheral blood samples are collected to measure PCT, interleukins (IL-1β, IL-6, IL-8), and TNF-α.

7. Length of hospital stay: comparison of the duration of hospitalization between groups.

2.5. Statistical analysis

Statistical analyses were conducted using SPSS software. For continuous variables, the Shapiro–Wilk test was first performed to assess normality. Data conforming to a normal distribution were described using mean ± standard deviation, and comparisons between groups were made using independent samples t test. For data not conforming to a normal distribution, the median and interquartile range were used for description, and comparisons were performed using one-way analysis of variance (ANOVA).

For categorical variables, data were presented as counts or percentages, and differences between groups were assessed using chi-square tests. A P value of <.05 was considered statistically significant, indicating that the observed differences were unlikely due to random error.

3. Results

3.1. Matching of baseline characteristics

Among the 263 patients who met the inclusion criteria, we performed 1:1 propensity score matching. As shown in Table 1, this process resulted in 62 patients in each group. After matching, there were no significant differences between the 2 groups in terms of age, gender, site of infection, SOFA score, APACHE II score, duration of sedation, mode of mechanical ventilation, cardiac function indicators, infection markers, and history of past illnesses. This matching process effectively eliminated the influence of these confounding factors on the subsequent outcome measures, ensuring that the baseline characteristics and severity of illness were comparable between the 2 groups. Thus, the different sedative drugs used became the primary variable for comparison.

Table 1.

Basic information of patients.

Variables	Before matching			After matching
	Experimental group	Control group	P	Experimental group	Control group	P
Total number of individuals	122	141		62	62
Age (years)	65.31 ± 9.12	60.21 ± 8.21	.001	62.11 ± 8.33	62.37 ± 7.69	.549
Gender			.336			.105
Male	62	80		29	38
Female	60	61		33	24
Infection site			.022			.283
Lung	52	61		30	29
Gastrointestinal tract	10	12		8	10
Biliary tract	11	22		6	11
Urinary system	21	33		7	8
Soft tissue	28	13		11	4
SOFA scores	9.51 ± 2.34	9.34 ± 2.41	.845	9.48 ± 2.11	9.34 ± 2.31	.645
APACHE II scores	20.44 ± 2.16	23.36 ± 2.31	.041	20.13 ± 2.33	19.98 ± 2.09	.546
Duration of sedation	0.25 ± 0.02	0.26 ± 0.04	.056	0.24 ± 0.02	0.24 ± 0.03	.445
Ventilator therapy			.902			.472
Invasive	51	60		30	34
Noninvasive	71	81		32	28
Myocardial function index
MYO	121.86 ± 9.56	126.33 ± 8.56	.031	121.96 ± 11.56	121.88 ± 10.89	.845
HR	121.36 ± 18.65	126.44 ± 17.26	.001	116.12 ± 16.16	118.13 ± 15.77	.547
BNP	811.31 ± 49.36	819.56 ± 49.99	.065	810.21 ± 50.16	821.13 ± 55.76	.515
Hs-Tn I	1.27 ± 0.69	1.25 ± 0.99	.041	1.27 ± 0.54	1.26 ± 0.61	.886
CK-MB	9.87 ± 2.21	9.89 ± 2.19	.844	9.88 ± 2.17	9.86 ± 2.21	.929
LVEF	41.96 ± 2.43	41.47 ± 2.01	.544	40.21 ± 2.13	41.51 ± 2.03	.187
LVESD	44.67 ± 4.31	46.21 ± 3.98	.101	46.98 ± 3.30	48.01 ± 3.03	.146
LVEDD	61.96 ± 3.21	63.03 ± 3.01	.113	63.32 ± 3.09	62.98 ± 4.04	.693
PCT	115.31 ± 15.36	116.21 ± 21.36	.095	116.12 ± 16.16	118.13 ± 15.77	.708
IL-1β	56.21 ± 20.36	54.36 ± 18.56	.041	54.66 ± 19.63	55.46 ± 20.21	.760
IL-6	86.35 ± 18.61	87.66 ± 21.26	.066	84.62 ± 21.44	85.33 ± 23.51	.794
IL-8	587.64 ± 121.46	572.36 ± 156.21	.001	574.54 ± 132.16	571.46 ± 144.21	.844
TNFα	196.12 ± 39.65	193.65 ± 45.36	.041	199.66 ± 40.26	202.64 ± 42.31	.692
Medical history
Hypertension (yes)	54	62	.345	32	36	.451
Diabetes (yes)	36	43	.113	36	38	.321
Propensity score ($\overline{X}\pm S$)	0.21 ± 0.56		.021	0.06 ± 0.31		.061

APACHE II = Acute Physiology and Chronic Health Evaluation II, BNP = B-type natriuretic peptide, CK-MB = creatine kinase-MB, HR = heart rate, hs-TnI = high-sensitivity troponin I, IL-1β, IL-6, IL-8 = interleukins, LVEDD = left ventricular end-diastolic diameter, LVEF = left ventricular ejection fraction, LVESD = left ventricular end-systolic diameter, MYO = myocardial enzyme levels, PCT = procalcitonin, SOFA = Sequential Organ Failure Assessment, TNF-α = tumor necrosis factor-alpha.

3.2. Comparison of the effects of different sedatives on patient heart rate

We first compared the HR of patients in the 2 groups before treatment, and on days 1, 3, and 7 of treatment, as shown in Table 2. Due to propensity score matching, there were no significant differences in HR between the groups before treatment (P > .05). However, significant differences were observed on days 1, 3, and 7 after treatment, with the experimental group having HRs of 93.22, 82.01, and 75.12, respectively, which were significantly lower than those of the control group (P < .05).

Table 2.

HR comparison between the 2 groups.

Group	Pretreatment	1 day after treatment	3 days after treatment	7 days after treatment
Experimental group (n = 62)	116.12 ± 16.16	93.22 ± 10.11*	82.01 ± 8.46*	75.12 ± 6.01*
Control group (n = 62)	118.13 ± 15.77	97.61 ± 9.66*	88.41 ± 7.88*	80.51 ± 8.24*
T value	-0.605	-3.322	-4.168	-3.405
P value	.547	.001	<.001	.001

HR = heart rate.

^* There were significant differences in the group compared with before treatment (P < .05).

3.3. Comparison of the effects of different sedatives on myocardial injury markers

There were no significant differences in hs-TnI and CK-MB between the 2 groups before treatment (P > .05), as shown in Table 3. On the first day of treatment, both groups exhibited a slight decrease in hs-TnI and a slight increase in CK-MB, but these changes were not statistically significant either within or between the groups. By days 3 and 7 of treatment, both hs-TnI and CK-MB levels had significantly decreased compared to baseline. MYO levels were also significantly lower on days 1, 3, and 7 compared to baseline. Notably, on day 3 posttreatment, the experimental group had significantly lower hs-TnI, CK-MB, and MYO levels compared to the control group. On day 7, CK-MB and MYO levels were significantly lower in the experimental group compared to the control group, while hs-TnI showed no significant difference between the 2 groups. The hs-TnI levels decreased significantly in both groups by day 3 (P < .001). By day 7, the levels were further reduced in the experimental group (0.41 ± 0.28 µg/L) compared to the control group (0.58 ± 0.43 µg/L), but this difference did not reach statistical significance (P = .170). However, CK-MB levels were significantly lower in the experimental group on both day 3 (6.76 ± 2.01 U/L) and day 7 (3.81 ± 1.81 U/L) compared to the control group (8.03 ± 2.40 U/L and 6.11 ± 1.98 U/L; P < .001).

Table 3.

Comparison of Hs-TnI and CK-MB in 2 groups.

Time	Hs-TnI (µg/L)		T value	P value	CK-MB (U/L)		T value	P value	MYO (µg/L)		T value	P value
	Experimental group (n = 62)	Control group (n = 62)			Experimental group (n = 62)	Control group (n = 62)			Experimental group (n = 62)	Control group (n = 62)
Pretreatment	1.27 ± 0.54	1.26 ± 0.61	0.144	0.886	9.88 ± 2.17	9.86 ± 2.21	0.089	0.929	121.96 ± 11.56	121.88 ± 10.89	0.012	0.845
1 day after treatment	1.26 ± 0.41	1.25 ± 0.78	0.066	0.948	9.91 ± 2.22	9.89 ± 2.31	0.073	0.942	87.09 ± 8.91*	88.31 ± 9.21*	0.045	0.758
3 days after treatment	0.75 ± 0.33*	0.99 ± 0.37*	-4.113	<0.001	6.76 ± 2.01*	8.03 ± 2.40*	-4.024	<0.001	60.12 ± 8.11*	65.32 ± 9.11*	-4.331	<0.001
7 days after treatment	0.41 ± 0.28*	0.58 ± 0.43*	-1.379	0.170	3.81 ± 1.81*	6.11 ± 1.98*	-5.697	<0.001	32.16 ± 7.12*	36.13 ± 6.97*	-4.132	<0.001

CK-MB = creatine kinase-MB, hs-TnI = high-sensitivity troponin I, MYO = myocardial enzyme levels.

^* There were significant differences in the group compared with before treatment (P < .05).

3.4. Comparison of the effects of different sedatives on heart failure indicators

We compared the differences in BNP levels between the 2 groups, as shown in Table 4. There were no significant differences in BNP levels between the groups before treatment and on the first day of treatment. However, on days 3 and 7 after treatment, BNP levels in the experimental group were significantly lower than those in the control group. Additionally, within-group comparisons showed that BNP levels decreased over time with treatment, and BNP levels on days 3 and 7 were significantly lower than baseline in both groups.

Table 4.

Comparison of BNP in 2 groups.

Group	Pretreatment	1 day after treatment	3 days after treatment	7 days after treatment
Experimental group (n = 62)	810.21 ± 50.16	822.22 ± 101.11	582.01 ± 178.46*	275.12 ± 136.41*
Control group (n = 62)	821.13 ± 55.76	817.61 ± 109.66*	688.31 ± 197.88*	389.51 ± 161.24*
T value	-0.652	-1.055	-4.519	-3.489
P value	.515	.293	<.001	.001

BNP = B-type natriuretic peptide.

^* There were significant differences in the group compared with before treatment (P < .05).

We also compared heart function indicators, as shown in Table 5. After 7 days of treatment, both groups showed significant increases in LVEF and significant decreases in LVESD and LVEDD compared to baseline. Moreover, the experimental group had significantly higher LVEF and significantly lower LVESD and LVEDD compared to the control group. On day 7, the experimental group had significantly lower BNP levels (275.12 ± 136.41 pg/mL) compared to the control group (389.51 ± 161.24 pg/mL, P = .001). LVEF was also significantly higher in the experimental group (51.36 ± 3.01%) compared to the control group (45.12 ± 2.95%, P < .001), indicating better cardiac function.

Table 5.

Comparison of cardiac function between the 2 groups.

	Group	Experimental group (n = 62)	Control group (n = 62)	T value	P value
LVEF (%)	Pretreatment	40.21 ± 2.13	41.51 ± 2.03	-1.326	.187
	7 days after treatment	51.36 ± 3.01*	45.12 ± 2.95*	7.362	<.001
LVESD (mm)	Pretreatment	46.98 ± 3.30	48.01 ± 3.03	-1.460	.146
	7 days after treatment	36.94 ± 2.22*	41.56 ± 2.98*	-6.052	<.001
LVEDD (mm)	Pretreatment	63.32 ± 3.09	62.98 ± 4.04	0.395	.693
	7 days after treatment	48.91 ± 2.13*	55.21 ± 3.36*	-8.489	<.001

LVEDD = left ventricular end-diastolic diameter, LVEF = left ventricular ejection fraction, LVESD = left ventricular end-systolic diameter.

^* There were significant differences in the group compared with before treatment (P < .05).

3.5. Comparison of the effects of different sedatives on inflammatory markers

We also compared inflammatory markers between the 2 groups, as shown in Table 6. The results for inflammatory factors were consistent across the groups. Compared to baseline, levels of PCT, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), and TNF-α were significantly reduced in both groups after 7 days of treatment. Additionally, on day 7 posttreatment, the experimental group exhibited significantly lower levels of all inflammatory markers compared to the control group.

Table 6.

Comparison of inflammatory indicators between the 2 groups.

	Group	Experimental group (n = 62)	Control group (n = 62)	T value	P value
PCT (µg/L)	Pretreatment	116.12 ± 16.16	118.13 ± 15.77	-0.375	.708
	7 days after treatment	75.12 ± 6.01*	80.51 ± 8.24*	-4.130	<.001
IL-1β (pg/mL)	Pretreatment	54.66 ± 19.63	55.46 ± 20.21	-0.306	.760
	7 days after treatment	19.36 ± 10.22*	30.24 ± 11.23*	-5.317	<.001
IL-6 (pg/mL)	Pretreatment	84.62 ± 21.44	85.33 ± 23.51	-0.262	.794
	7 days after treatment	34.31 ± 18.23*	48.14 ± 18.99*	-4.441	<.001
IL-8 (pg/mL)	Pretreatment	574.54 ± 132.16	571.46 ± 144.21	0.197	.844
	7 days after treatment	236.54 ± 111.34*	316.77 ± 108.36*	-5.831	<.001
TNF-α (pg/mL)	Pretreatment	199.66 ± 40.26	202.64 ± 42.31	-0.398	.692
	7 days after treatment	82.21 ± 24.41*	110.22 ± 28.21*	-5.578	<.001

IL-1β, IL-6, IL-8 = interleukins, PCT = procalcitonin, TNF-α = tumor necrosis factor-alpha.

^*mean comparison with pretreatment P < 0.05.

3.6. Comparison of length of hospital stay between sedative groups

Finally, we compared the length of hospital stay between the 2 groups, as shown in Table 7. There were no significant differences in the length of hospital stay between the experimental and control groups (P > .05), with the experimental group staying an average of 22.31 ± 7.56 days compared to 23.15 ± 6.51 days in the control group.

Table 7.

Days of hospitalization in the 2 groups.

Group	Days of hospitalization	T value	P value
Experimental group (n = 62)	22.31 ± 7.56	-0.47	.64
Control group (n = 62)	23.15 ± 6.51

4. Discussion

Sepsis is a life-threatening condition that often arises during the progression of severe diseases such as major surgical procedures, extensive burns, poisoning, and severe heatstroke, potentially leading to septic shock, multiple organ dysfunction syndrome, and even death.^[7–9] The heart is one of the most commonly affected organs in sepsis, with about 50% of patients experiencing myocardial injury, and mortality rates exceeding 70% in those with myocardial involvement.^[10] The disease progression of sepsis with myocardial injury is highly complex. Current treatments focus on symptomatic support, including infection control, fluid resuscitation, organ protection, and maintaining acid–base and electrolyte balance. Therefore, there is an urgent need for effective therapeutic agents to significantly reduce mortality, improve prognosis, and enhance quality of life in patients with sepsis and myocardial injury.^[11,12] Dexmedetomidine, a sedative, has recently been shown not only to provide effective sedation but also to reduce inflammatory marker levels, exert anti-inflammatory effects, and protect vital organs.

The data analysis in this study reveals that patients with sepsis and myocardial injury (both dexmedetomidine and midazolam groups) exhibited significantly elevated levels of HR, myocardial injury markers (hs-TnI and CK-MB), inflammatory markers (PCT, IL-1β, IL-6, IL-8, and TNF-α), and heart failure indicators (BNP, LVESD, and LVEDD) compared to the control group before treatment. Conversely, LVEF was significantly reduced, indicating that myocardial injury is commonly associated with sepsis, consistent with previous studies.^[13–22] The pathophysiological process of sepsis with myocardial injury is complex, with the exact mechanisms remaining unclear. Based on current research, the following mechanisms are considered: (1) impact of inflammatory markers: sepsis triggers the production of large amounts of inflammatory cytokines such as TNF-α and IL-1β, which activate macrophages to secrete additional inflammatory factors like IL-6 and IL-8, leading to a cascade of inflammatory responses. This results in myocardial fibrosis and dilation, cellular swelling, mitochondrial dysfunction, endoplasmic reticulum stress, Ca²⁺ overload, and apoptosis of myocardial cells, all of which negatively affect myocardial function.^[14,15] (2) Hemodynamic changes: excessive release of nitric oxide (NO) and reduced responsiveness to vasoconstrictors cause excessive dilation of microcirculatory vessels, decreased vascular tone, endothelial dysfunction, and increased capillary permeability. This further leads to coagulation disorders, microthrombi formation, inadequate tissue perfusion, reduced cardiac preload, and decreased cardiac compliance.^[16,17] (3) Cellular metabolism alterations: the energy required for myocardial contraction is primarily supplied by fatty acid β-oxidation in the mitochondria. Sepsis can increase myocardial cell permeability, cause mitochondrial membrane damage, disrupt oxidative phosphorylation, and reduce kinase activity, leading to a significant drop in ATP synthesis and severe energy depletion.^[18,19] Additionally, mitochondrial dysfunction results in pathological hypoxia and accelerates myocardial cell death.^[20] (4) Role of Ca²⁺: the release of various cytokines during sepsis leads to the leakage of Ca²⁺ from the sarcoplasmic reticulum into the cells, disrupting Ca²⁺ homeostasis. Maintaining Ca²⁺ balance is crucial for cardiac structure and contractile function. Ca²⁺ overload weakens myocardial contractility and can even lead to heart failure.^[21,22] (5) Effects on neural conduction: during sepsis, the renin–angiotensin–aldosterone system (RAAS) is excessively activated, leading to increased angiotensin-converting enzyme activity and elevated levels of angiotensin. This exacerbates myocardial ischemia and hypoxia.^[23]

Most researchers currently believe that sepsis-related myocardial injury is primarily caused by the excessive release of inflammatory cytokines. During sepsis, the inflammatory response is excessively activated, with both pro-inflammatory and anti-inflammatory factors becoming abnormally active, culminating in a “cytokine storm.”^[24,25] This storm involves a positive feedback loop where cytokines are increasingly generated, activated, and released, further exacerbating myocardial damage. Key representatives of this phenomenon are IL-8 and TNF-α, which are crucial for diagnosing, monitoring, and prognosticating sepsis.^[24] Studies have shown that IL-8 levels directly affect leukocyte activation at infection sites.^[24] In this study, IL-8 levels were significantly elevated in patients with sepsis and myocardial injury, remaining several times above normal values even after 7 days of treatment. TNF-α, an important pro-inflammatory cytokine in early inflammatory responses, activates cytokine networks, stimulating neutrophils and lymphocytes in patients with sepsis and myocardial injury. It contributes to the “cytokine storm” along with other cytokines and participates in the immune response.^[25] Additionally, TNF-α promotes the production of large amounts of oxygen free radicals, damaging vascular endothelial cells, disrupting myocardial structure, increasing cardiac preload, disturbing calcium homeostasis, and impairing cardiac contractility.^[26]

PCT is produced in response to inflammation or sepsis, stimulated by inflammatory mediators or toxins, and is highly specific and sensitive for the diagnosis and detection of infections. Research indicates that PCT levels rise with the progression of the condition, suggesting that PCT is associated with changes in the severity of sepsis.^[27] In mouse models of sepsis, studies by Yao et al^[28] and Kim et al^[29] have shown that dexmedetomidine treatment significantly reduces TNF-α, IL-1β, and IL-6 levels, decreases the expression of the TLR-4/NF-κB pathway, reduces the incidence of septic shock, and improves mouse survival. Xiandan Wu et al^[30] demonstrated that dexmedetomidine effectively reduces inflammation in ICU patients with mechanical ventilation-induced sepsis while also providing cardioprotective effects. This study found that, in patients with sepsis combined with myocardial injury, the levels of PCT, IL-1β, IL-6, IL-8, and TNF-α on the 3rd and 7th day of treatment significantly decreased compared to before treatment. Compared to midazolam, the reduction in these indicators was more pronounced in the dexmedetomidine treatment group. Although all patients received standard antibiotic therapy, which led to a decrease in inflammatory markers, the decline was more significant in the dexmedetomidine group, while midazolam had no anti-inflammatory effect. This suggests that dexmedetomidine can effectively reduce inflammation markers in patients with sepsis combined with myocardial injury, mitigate the inflammatory response, and may exert cardioprotective effects by improving mitochondrial function in myocardial cells, alleviating endoplasmic reticulum metabolic abnormalities, and reducing myocardial cell apoptosis. However, this study found no statistically significant difference in hospital stay duration between the control and experimental groups, indicating that dexmedetomidine does not shorten hospital stay. Despite improvements in various indicators, the complex pathophysiological processes of sepsis combined with myocardial injury, inflammatory cytokine storms, and multi-organ dysfunction may render dexmedetomidine alone insufficient to significantly reduce hospital stay. Additionally, the final outcomes may be influenced by individual differences and other unknown factors.

5. Limitations of the study

This study has several limitations. First, it is a single-center retrospective study, which may limit the generalizability of the findings. The relatively small sample size and short-term follow-up (7 days) also restrict the assessment of long-term outcomes. While midazolam was used as a control, it may not be the optimal comparator since it lacks cardioprotective effects. Randomization was not employed, meaning residual confounding could still exist despite the use of propensity score matching. Additionally, the study did not account for the impact of other medications, such as antibiotics and vasopressors, that may have influenced patient outcomes. Future multi-center, randomized studies with longer follow-up are needed to confirm these findings and assess the long-term efficacy of dexmedetomidine in patients with sepsis and myocardial injury.

6. Conclusion

Sepsis with myocardial injury is a complex and life-threatening condition. Dexmedetomidine can reduce heart rate and inflammatory cytokine levels in patients with sepsis combined with myocardial injury, protect myocardial cells, and improve cardiac function. Dexmedetomidine shows potential in treating sepsis with myocardial injury. Future research needs to delve into the long-term efficacy and safety of dexmedetomidine to provide a more effective treatment option for patients with sepsis and myocardial injury. Additionally, further investigations should explore the combination of dexmedetomidine with other therapeutic agents, such as vasopressors and antibiotics, to determine its synergistic effects on patient outcomes. Evaluating various dosing regimens and the role of dexmedetomidine in different stages of sepsis could also help optimize treatment strategies. These directions will contribute to a deeper understanding of dexmedetomidine’s long-term efficacy and safety in managing sepsis-related myocardial injury.

Author contributions

Conceptualization: Xiaomin Si, Zhonglue Huang.

Data curation: Xiaomin Si, Zhonglue Huang, Zhanqun Pan.

Formal analysis: Xiaomin Si, Zhonglue Huang, Zhanqun Pan.

Investigation: Xiaomin Si.

Methodology: Xiaomin Si.

Validation: Zhanqun Pan.

Visualization: Zhanqun Pan.

Writing – original draft: Xiaomin Si, Zhonglue Huang, Zhanqun Pan.

Writing – review & editing: Xiaomin Si, Zhonglue Huang, Zhanqun Pan.