Effects of dexmedetomidine on renal function in patients with septic shock

Abstract

This study was to observe the effects of dexmedetomidine against acute kidney injury in patients with septic shock. A prospective randomized controlled trial (RCT) was conducted in which 80 patients with septic shock admitted in Department of Critical Care Medicine of the Affiliated Hospital of Chengdu University from June 2015 to January 2017 were divided into experimental group and control group. The patients in both groups received basic treatment for septic shock, and the patients in the experimental group were given intravenous injection of dexmedetomidine, maintained with 0.1–0.2 µg kg⁻¹ h⁻¹ for 5 days. In both groups, the changes in the levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, serum creatinine (SCr), cystatin C (Cys C), and β2-microglobulin (β2-MG) were determined before treatment and 1, 3, and 5 days after treatment. At 5 days after treatment, Cys C, β2-MG, and SCr were significantly decreased in both groups (P < 0.05), and the degree of decrease in the experimental group was more obvious (P < 0.05). At 1, 3, and 5 days after treatment, IL-6 and TNF-α were significantly decreased in both groups (P < 0.05) and the degree of decrease in the experimental group was more obvious (P < 0.05). Dexmedetomidine has certain renal protective effect in patients with septic shock, and its mechanism is possibly related to the regulation and improvement of uncontrolled inflammatory response.

Septic shock is a systemic inflammatory response caused by infection. It can easily develop into multiple organ dysfunction, and the incidence of acute kidney injury (AKI) is high, which results in poor prognosis. At present, there is still lack of effective methods and drugs for the prevention and treatment of AKI. Dexmedetomidine (Dex) is a sedative and analgesic drug commonly used in intensive care unit (ICU). Recent studies have shown that Dex has anti-inflammatory and protective effects on organs. Therefore, we aimed to investigate the effect of Dex on renal function in patients with septic shock by examining the changes of renal function indexes and inflammatory indexes.

Data and methods

Case inclusion and exclusion criteria

A prospective randomized controlled clinical trial was conducted in the Critical Care Unit of Chengdu University Affiliated Hospital from June 2015 to January 2017. This study confirmed the medical ethics standard and was approved by the ethics committee of our hospital.

Inclusion criteria

All patients are older than 18 years; the diagnosis of septic shock is according to 2012 KIDGO-AKI international guidelines for severe sepsis and septic shock; the diagnosis of AKI is according to 2012 KIDGO-AKI international guidelines; patients are informed about the whole protocol of the study.

Exclusion criteria

The exclusion criteria are as follows: (1) kidney-related diseases with renal function damage before treatment; (2) patients that are judged to die, combined with severe lung, heart, liver, and renal dysfunction; (3) combined with tachyarrhythmia, severe heart block, heart rate (HR) < 50 beats/min; (4) intolerance to Dex (allergy, severe hypotension); (5) no response to treatment and blood pressure could not be maintained to the goal of recovery; and (6) death or failed to adhere to the systemic treatment.

Groups and treatment

All patients were randomly divided into the experimental group and the control group; patients in the treatment group were in accordance with the “2012 international guidelines for severe sepsis and septic shock treatment,” including early liquid resuscitation, anti-inflammatory therapy, and sedative and analgesic treatment. Dex was given on the basis of (200 g + 0.9 NS 50 ml prepared in 0.1–0.2 g kg⁻¹ h⁻¹; Jiangsu Hengrui Medicine Co. Ltd, 200 g/) by trace pump continuous intravenous infusion for 5 days.

Observation indexes

For patients in the two groups, acute physiology and chronic health evaluation II (APACHE II) score was were recorded, all the general information, such as sex and age, was collected, and the related information before treatment (D₀) and 1 day (D₁), 3 days (D₃), and 5 days (D₅) after treatment was also collected. The blood samples were collected to detect serum creatinine (SCr), serum cystatin C (Cys C), β2-microglobulin (β2-MG), and other indicators; using enzyme-linked immunosorbent assay (ELISA), the interleukin (IL)-1 and tumor necrosis factor (TNF)-α levels (D₀) before and 1 (D₁), 3 (D₃), and 5 (D₅) days after treatment were detected.

Statistical analysis

SPSS 18 statistical software was used to analyze the data, and all the measured data were expressed as mean ± standard deviation (x ± s). t test was used. The counting data were tested by χ², and P < 0.05 was used to indicate statistically significant difference.

Results

Renal function indexes are shown in Table 1. The Cys C, β2-MG, and SCr levels were almost the same between the two groups before treatment and there was no significant difference (P > 0.05). At 1 day after treatment, the Cys C, β2-MG, and SCr levels in two groups were significantly higher than those before treatment; in the control group, the rate of increase was even higher (P < 0.05), and the difference was statistically significant. At 3 days after treatment, the Cys C, β2-MG, and SCr levels in the control group were increasing gradually compared to those at 1 day after treatment. In the experimental group, Cys C, β2-MG, and SCr were higher than those at 1 day after treatment (P < 0.05), and the difference was statistically significant. At 5 days after treatment, the Cys C, β2-MG, and SCr levels in the two groups were lower than those before treatment (P < 0.05), but the experimental group was more obvious than the control group (P < 0.05). Changes in inflammatory markers are shown in Table 2.

Table 1.

The renal functions of the two groups.

Indexes	Groups	D0	D1	D3	D5
SCr (µmol/L)	Control group	86.5 ± 36.2	126.3 ± 27.6	132.3 ± 26.4	116.1 ± 30.5
	Experimental group	89.0 ± 33.4	113.2 ± 28.9*	104.3 ± 22.1*	90.3 ± 27.6*
Cys C (mg/L)	Control group	2.2 ± 0.6	4.7 ± 1.8	4.6 ± 1.2	2.5 ± 0.6
	Experimental group	2.4 ± 0.5	3.9 ± 1.6*	3.0 ± 1.7*	1.5 ± 0.5*
β2-MG (mg/L)	Control group	4.2 ± 1.3	6.4 ± 1.4	6.8 ± 1.5	4.5 ± 1.8
	Experimental group	4.4 ± 1.1	5.5 ± 1.7*	4.6 ± 1.2*	3.2 ± 1.3*

SCr: serum creatinine; Cys C: serum cystatin C; β2-MG: β2-microglobulin.

*

P < 0.05 compared with the control group.

Table 2.

The changes of inflammatory indexes at different time points.

Indexes	Groups	D0	D1	D3	D5
IL-6 (ng/L)	Control group	87.4 ± 17.6	82.8 ± 13.2	78.9 ± 10.5	60.3 ± 14.7
	Experimental group	88.7 ± 14.8	72.4 ± 14.1*	62.3 ± 12.3*	51.2 ± 15.4*
TNF-α (ng/L)	Control group	76.2 ± 13.5	71.5 ± 10.8	62.1 ± 7.6	57.9 ± 6.4
	Experimental group	77.1 ± 12.0	65.5 ± 11.2*	56.5 ± 8.1*	45.5 ± 5.5*

IL: interleukin; TNF: tumor necrosis factor.

*

P < 0.05 compared with the control group.

There was no significant difference in the levels of IL-6 and TNF-α before treatment between the two groups (P > 0.05). The values at 1, 3, and 5 days after treatment decreased more than those before treatment; the values decreased significantly in the experimental group, and the difference was statistically significant (P < 0.05).

Discussion

AKI is caused by various causes of renal ischemia–reperfusion injury which can lead to permanent and complete loss of renal function. Dex is a highly selective alpha-2 adrenergic receptor agonist with sedative and analgesic effects, which is currently used mainly for ICU sedation and clinical anesthesia. It was found that the renal injury in mice with renal ischemia–reperfusion injury was significantly reduced by Dex. The use of Dex in patients undergoing cardiopulmonary bypass had significantly reduced the impairment of acute renal function. ¹ Cys C has become one of the early indicators of detection and identification of AKI with high sensitivity. β2-microspheres can be filtered freely by glomerulus. The study found that patients with septic shock on the basis of regular treatment combined with Dex decreased Cys C, β2-MG, and SCr levels significantly faster compared to the control group, and the difference was statistically significant, suggesting that Dex has certain protective effect on renal injury.

Dex inhibits sympathetic overactivity, reduces the direct damage of sympathetic overactivity to the kidneys, and maintains the renal blood flow and glomerular filtration rate as reported by Ji et al. ¹ Many studies show that Dex can significantly reduce inflammatory animal models such as the heart, kidney, brain, and intestine ischemia–reperfusion injury after inflammation. ² This study showed that, after infusion of Dex in patients with septic shock, the serum IL-6 and TNF-α levels were significantly lower than those in the control group and showed significantly reduced inflammatory reaction, which can alleviate the loss of renal function.