Dexmedetomidine Reduces Atrial Fibrillation After Adult Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Dexmedetomidine has been shown to have antiarrhythmic effects by exhibiting sympatholytic properties and activating the vagus nerve in preclinical studies. Results from clinical trials of dexmedetomidine on atrial fibrillation (AF) following adult cardiac surgery are controversial. MATERIALS AND METHODS: We searched EMBASE, PubMed and Cochrane CENTRAL databases for randomized controlled trials (RCTs) comparing the antiarrhythmic effect of dexmedetomidine versus placebo or other anesthetic drugs in adult patients undergoing cardiac surgery. The primary outcome was the incidence of AF. The secondary outcomes were ventricular arrhythmias [ventricular fibrillation (VF), ventricular tachycardia (VT)], mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay, and hospital length of stay, and all-cause mortality. RESULTS: Thirteen trials with a total of 1684 study patients were selected. Compared with controls, dexmedetomidine significantly reduced the incidence of postoperative AF [odds ratio (OR) 0.75; 95% confidence interval (CI) 0.58-0.97; P = 0.03] and VT (OR 0.23; 95% CI 0.11-0.48; P < 0.0001). No significant difference for the incidence of VF existed (OR 0.80; 95% CI 0.21-3.03; P = 0.74). There was no significant difference between groups in MV duration [weighted mean difference (WMD) - 0.10; 95% CI - 0.42 to 0.21; P = 0.52], postoperative ICU stay (WMD - 0.49; 95% CI - 2.64 to 1.66; P = 0.65), hospital stay (WMD - 0.01; 95% CI - 0.16 to 0.13; P = 0.88) and mortality (OR 0.59; 95% CI 0.15-2.37; P = 0.46). CONCLUSIONS: Perioperative administration of dexmedetomidine in adult patients undergoing cardiac surgery reduced the incidence of postoperative AF and VT. But there was no significant difference in incidence of VF, MV duration, ICU stay, hospital stay and mortality.

[Validation of a septic myocardial inhibition model by intraperitoneal injection of endotoxin in rats].

OBJECTIVE: To establish septic myocardial inhibition rat model by echocardiography. METHODS: Twenty adult male Sprague-Dawley (SD) rats were divided into control group and model group according to the random number table method, with 10 rats in each group. The rat model of septic myocardial inhibition was reproduced by intraperitoneal injection of 10 mg/kg lipopolysaccharide, while the control group was given the same volume of saline. The left ventricular end-diastolic diameter (LVDd), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic diameter (LVDs), left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), right ventricular end-diastolic diameter (RVDd), right ventricular end-systolic diameter (RVDs), heart rate (HR), positive pulmonary artery flow rate and aortic flow rate were measured at 8 hours after model establishment by echocardiography. Then the rats were sacrificed to harvest serum and myocardial tissue. The levels of serum tumor necrosis factor-α (TNF-α), nuclear factor-ΚB (NF-ΚB), interleukin-1 (IL-1), cardiac troponin I (cTnI) and B-type brain natriuretic peptide (BNP) were measured by enzyme linked immunosorbent assay (ELISA). The mRNA expressions of TNF-α, IL-1 and NF-ΚB in myocardium were detected by real-time polymerase chain reaction (real-time PCR). The pathological changes of myocardium were observed by hematoxylin-eosin (HE) staining under light microscope. RESULTS: Compared with control group, myocardial inhibition was obviously observed in model group, manifesting as enlargement of overall shape of heart, and prominent increase of HR (bpm: 449.0±21.1 vs. 356.7±23.3, P < 0.01); left ventricular and right ventricular functions were affected, LVDd, LVDs, LVEDV, LVESV were enlarged [LVDd (mm): 10.03±0.95 vs. 7.04±0.71, LVDs (mm): 5.95±0.71 vs. 3.07±0.05, LVEDV (mL): 2.11±0.53 vs. 0.81±0.21, LVESV (mL): 0.51±0.16 vs. 0.07±0.01, all P < 0.05], LVEF was significantly decreased (0.760±0.046 vs. 0.901±0.025, P < 0.01), RVDd was significantly increased (mm: 4.48±0.58 vs. 3.22±0.20, P < 0.05), and positive pulmonary artery velocity was significantly decreased (cm/s: 64.2±9.3 vs. 89.0±0.8, P < 0.05). Compared with control group, the levels of serum NF-ΚB, TNF-α, IL-1, BNP and cTnI in model group were significantly increased [NF-ΚB (ng/L): 103.84±6.55 vs. 57.29±41.34, TNF-α (ng/L): 1 198.32±164.07 vs. 835.45±24.01, IL-1 (ng/L): 1 089.90±221.96 vs. 746.19±165.83, BNP (ng/L): 1 097.36±293.84 vs. 454.71±197.79, cTnI (ng/L): 6 938.59±1 400.21 vs. 3 731.90±1 349.31, all P < 0.01], the mRNA expressions of TNF-α, NF-ΚB and IL-1 in myocardial tissue were significantly increased (2-ΔΔCT: 1.50±0.42 vs. 0.71±0.40, 1.10±0.17 vs. 0.63±0.06, 1.77±0.67 vs. 0.10±0.03, all P < 0.05). It was shown by HE staining that the structure of myocardial tissue in control group was distinct, the arrangement of myocardial fibers was neat, and transverse was clear; the structure of myocardial tissue in model group was loose, blurred, and the cells were swollen, with obvious pathological changes. CONCLUSIONS: Cardiac function was assessed by echocardiography, expression of inflammatory factors, myocardial markers and pathological changes. It was verified that intraperitoneal injection of 10 mg/kg endotoxin could successfully prepare a rat model of septic myocardial inhibition.

Effect of interleukin-31 on septic shock through regulating inflammasomes and interleukin-1ß.

Sepsis with severe systemic inflammation remains a great challenge for the intensive care unit in clinics. Although biomarkers have been identified to diagnose, monitor and predict these syndromes, novel therapeutic approaches are required for the amelioration of symptoms of sepsis and septic shock. The present study demonstrated that interleukin (IL)-31 was able reduce the mortality rate of lipopolysaccharide (LPS)-induced sepsis with the reduction of inflammatory cytokines in the sera. IL-31 also inhibited IL-1ß production in the peritoneal lavage fluid in LPS-induced or cecal ligation and puncture-induced sepsis. The in vitro mechanism responsible for IL-31 regulation on peritoneal IL-1ß activation following LPS challenge was explored. It was demonstrated that IL-1ß secretion was suppressed by IL-31 treatment from LPS-challenged peritoneal macrophages following adenosine triphosphate stimulation, which is an activator of NLR family, pyrin domain-containing 3 (NLRP3). Furthermore, IL-31 inhibited the expression of NLRP3 at the transcriptional level. In human THP-1 cells, anti-IL-31/anti-IL-31 receptor (R) neutralizing antibody enhanced NLRP3 expression as well as IL-1ß activation, suggesting a role of the IL-31-IL-31R-NLRP3-IL-1ß signaling axis in the physiological status of sepsis. On the other hand, IL-31 displayed a negative effect on the NLRP1 inflammasome, but not on NLRP3 on the LPS-primed human peripheral blood monocytes, resulting in reduction of the inflammatory cytokine, tumor necrosis factor (TNF)-α, in the supernatant. Taken together, the present data implied that T helper 2-type cytokine, IL-31, may be a promising therapeutic option for treatment of sepsis and septic shock in clinics.

Dexmedetomidine prevents acute kidney injury after adult cardiac surgery: a meta-analysis of randomized controlled trials.

BACKGROUND: Dexmedetomidine has been shown to confer direct renoprotection by stabilizing the sympathetic system, exerting anti-inflammatory effects and attenuating ischemia/reperfusion (I/R) injury in preclinical studies. Results from clinical trials of dexmedetomidine on acute kidney injury (AKI) following adult cardiac surgery are controversial. METHODS: We searched EMBASE, PubMed, and Cochrane CENTRAL databases for randomized controlled trials (RCTs) comparing the renal effect of dexmedetomidine versus placebo or other anesthetic drugs in adult patients undergoing cardiac surgery. The primary outcome was the incidence of AKI. The secondary outcomes were mechanical ventilation (MV) duration, intensive care unit (ICU) stay and hospital length of stay(LOS), and postoperative mortality (in-hospital or within 30 days). RESULTS: Ten trials with a total of 1575 study patients were selected. Compared with controls, dexmedetomidine significantly reduced the incidence of postoperative AKI [68/788 vs 97/787; odds ratio(OR), 0.65; 95% confidence interval (CI), 0.45-0.92; P = 0.02; I2 = 0.0%], and there was no difference between groups in postoperative mortality (4/487 vs 11/483; OR, 0.43; 95% CI, 0.14-1.28; P = 0.13; I2 = 0.0%), MV duration [in days; n = 1229; weighted mean difference(WMD), -0.22; 95% CI, -2.04 to 1.70; P = 0.81], ICU stay (in days; n = 1363; WMD, -0.85; 95% CI, -2.14 to 0.45; P = 0.20), and hospital LOS (in days; n = 878; WMD, -0.24; 95% CI, -0.71 to 0.23; P = 0.32). CONCLUSIONS: Perioperative administration of dexmedetomidine in adult patients undergoing cardiac surgery may reduce the incidence of postoperative AKI. Future trials are needed to determine the dose and timing of dexmedetomidine in improving outcomes, especially in patients with decreased baseline kidney function.