The pathogenesis of septic myocardial depression is complicated. Mitochondrial dysfunction has been suggested to be one of the main reasons for the reduced cardiac function. As melatonin is an antioxidant with the potential to scavenge radicals in mitochondria, we therefore employed a sepsis model, that is, cecal ligation and double puncture (CLP) in rats, to study the melatonin effects on: (i), myocardial mitochondrial function; (ii), heart systolic function; and (iii), prognosis of septic rats. We demonstrate that melatonin treatment (30 mg/kg, 3, 6, 12, 18, 24 hr after CLP) (i) improved myocardial cytochrome c oxidase (CcOX) activity and blood lactate level, (ii) attenuated heart dysfunction with a higher left ventricular ejection fraction (EF), and (iii) promoted 48-h survival of the rats compared to CLP animals with no melatonin treatment. In conclusion, our results show that rat myocardial mitochondrial CcOX activity was depressed during severe sepsis accompanied by myocardial depression characterized by the decline of EF. In septic rats, melatonin increased the CcOX activity, improved heart systolic function, and lowered mortality rate. The clinical use of melatonin in septic myocardial depression should be tested in the future.

To explore the mechanism of mitochondrial uncoupling protein 2 (UCP2) mediating the protective of melatonin when septic cardiomyopathy. UCP2 knocked out mice and cardiomyocytes were used to study the effect of melatonin in response to LPS. Indicators of myocardial and mitochondria injury including mitochondrial membrane potential, mitochondrial permeability transition pore, calcium loading, ROS, and ATP detection were assessed. In addition cell viability and apoptosis as well as autophagy-associated proteins were evaluated. Melatonin was able to protect heart function from LPS, which weakened in the UCP2-knockout mice. Consistently, genipin, a pharmacologic inhibitor of UCP2, augmented LPS-induced damage of AC16 cells. In contrast, melatonin upregulated UCP2 expression and protected the cells from the changes in morphology, mitochondrial membrane potential loss, mitochondrial Ca2+ overload, the opening of mitochondrial permeability transition pore, and subsequent increased ROS generation as well as ATP reduction. Mitophagy proteins (Beclin-1 and LC-3β) were increased while apoptosis-associated proteins (cytochrome C and caspase-3) were decreased when UCP2 was up-regulated. In conclusion, UCP2 may play a protecting role against LPS by regulating the balance between autophagy and apoptosis of cardiomyocytes, and by which mechanisms, it may contribute to homeostasis of cardiac function and cardiomyocytes activity. Melatonin may protect cardiomyocytes through modulating UCP2.

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Background:Jejunal feeding tube allows the nutrition of critical care patients more easy and safe. However, its placement remains a challenge. This study aimed to introduce a jejunal feeding tube through an ultrasound-guided antral progressive water injection method and subsequently to examine its efficacy.Methods:Between April 2016 and April 2017, 54 patients hospitalized in the Department of Critical Care Medicine, Peking Union Medical College Hospital, China who needed nutritional support through a jejunal feeding tube were recruited for this study. Patients who applied ultrasound-guided antral progressive water injection method were classified into the experimental group. Patients who applied conventional method were registered as control group.Results:No significant differences were found in age, body mass index, and Acute Physiology and Chronic Health Evaluation score, but a significant difference in operation time was found between the experimental group and the control group. Of the 24 individuals in the control group, 17 displayed clear catheter sound shadows once the tube entered the esophagus. In comparison, of the 30 individuals in the experimental group, all harbored catheter sound shadows through the esophageal gas injection method. Subsequent observation revealed that in the control group (via ultrasonographic observation), 15 individuals underwent successful antral tube entry, for a success rate of 63%. In the experimental group (via antral progressive water injection), 27 individuals underwent successful antral tube entry, for a success rate of 90%. There was a significant difference between the success rates of the two groups (χ2 = 5.834, P = 0.022).Conclusion:The antral progressive water injection method for the placement of a jejunal feeding tube is more effective than the traditional ultrasonic placement method.

Background: Acute kidney injury (AKI) is a serious complication in critically ill patients with septic shock treated in the intensive care unit. Renal replacement therapy (RRT) is a treatment for severe AKI; however, the time of initiation of RRT and factors that affect the recovery of kidney function remains unclear. This study was to explore whether early initiation of RRT treatment for fluid management to reduce central venous pressure (CVP) can help to improve patients’ kidney function recovery. Methods: A retrospective analysis of septic patients who had received RRT treatment was conducted. Patients received RRT either within 12 h after they met the diagnostic criteria of renal failure (early initiation) or after a delay of 48 h if renal recovery had not occurred (delayed initiation). Parameters such as patients’ renal function recovery at discharge, fluid balance, and levels of CVP were assessed. Results: A total of 141 patients were eligible for enrolment: 40.4% of the patients were in the early initiation group (57 of 141 patients), and 59.6% were in the delayed initiation group (84 of 141 patients). There were no significant differences in the characteristics at baseline between the two groups, and there were no differences in 28-day mortality between the two groups (χ 2 = 2.142, P = 0.143); however, there was a significant difference in the recovery rate of renal function between the two groups at discharge (χ 2 = 4.730, P < 0.001). More importantly, early initiation of RRT treatment and dehydration to reduce CVP are more conducive to the recovery of renal function in patients with AKI. Conclusion: Compared with those who received delayed initiation RRT, patients who received early-initiation RRT for dehydration to reduce CVP have enhanced kidney function recovery.

Objective To investigate the effect of focused ultrasonography on clinical outcomes of septic shock. Methods Patients with septic shock were randomized into an integrated cardiopulmonary ultrasonography (ICUS) group and conventional (CON) group. Within 1 hour of admission, the ICUS group underwent ICUS examination for hemodynamic decision-making, while the CON group received standard treatment. The primary endpoint was 28-day mortality after admission. The secondary endpoints were cumulative fluid administration in the first 6, 24, and 72 hours; use of vasoactive drugs; lactate clearance; duration of ventilation; and ICU stay. Results Ninety-four qualified patients were enrolled (ICUS group, 49; CON group, 45). ICUS showed no significant effect on 28-day mortality. Within the initial 6 hours, the ICUS group tended to have a higher fluid balance and fluid intake than the CON group. The duration of vasopressor support was shorter in the ICUS group. There were no differences in the cumulative fluid infusion within 24 or 72 hours, lactate clearance, ICU stay, or duration of ventilation. Conclusions The initially focused ICUS did not affect the clinical outcomes of septic shock, but it tended to be associated with a higher fluid balance within the initial 6 hours and shorter duration of vasopressor support.

Introduction Right ventricle (RV) dilation in combination with elevated central venous pressure (CVP), which is a state of RV congestion, is seen as a sign of RV failure (RVF). On the other hand, RV systolic function is usually assessed by tricuspid annular plane systolic excursion (TAPSE) and fractional area change (FAC). This study aimed to investigate the prevalence and prognostic value of RVF and RV systolic dysfunction (RVSD) in septic patients. Methods Mechanically ventilated sepsis and septic shock patients were included. We collected haemodynamic and echocardiographic parameters as well as prognostic information including mechanical ventilation duration, length of ICU stay and 30-day mortality. RVF was defined as a right and left ventricular end-diastolic area ratio ≥ 0.6 in combination with CVP ≥ 8 mmHg. RVSD was defined as TAPSE < 16 mm or FAC < 35%. Results A total of 215 patients were enrolled in this study, and the patients were divided into 4 groups: patients with normal RV function (normal, n = 101), patients with RVF but without RVSD (RVF only, n = 38), patients with RVSD but without RVF (RVSD only, n = 44), and patients with combined RVF–RVSD (RVF/RVSD, n = 32). The RVF/RVSD group and RVSD only group had a lower cardiac index than the RVF only group and normal groups (p < 0.05). At 30 days after ICU admission, 50.0% of patients had died in the RVF/RVSD group, which was much higher than the mortality in the RVF only group (13.2%) and normal group (13.9%) (p < 0.05). In a Cox regression analysis, the presence of RVF/RVSD was independently associated with 30-day mortality (HR 3.004, 95% CI:1.370–6.587, p = 0.006). In contrast, neither the presence of RVF only nor the presence of RVSD only was associated with 30-day mortality (HR 0.951, 95% CI:0.305–2.960, p = 0.931; HR 1.912, 95% CI:0.853–4.287, p = 0.116, respectively). Conclusion The presence of combined RVF–RVSD was associated with 30-day mortality in mechanically ventilated septic patients. Additional studies are needed to confirm and expand this finding.

ObjectiveTo perform early assessment of sepsis-induced myocardial dysfunction (SIMD) using strain/stress echocardiography.MethodsA canine model of SIMD was established using intravenous injection of lipopolysaccharide (LPS, 2 mg/kg). Thirteen dogs were included, comprising an LPS-treated SIMD group (n = 7) and saline control group (n = 6). SIMD was assessed at various time-points using cardiac measurements including haemodynamics and echocardiography.ResultsSystolic and radial ventricular wall stress and circular ventricular wall stress (WSsc) were significantly lower in the sepsis group versus the control group at all time-points. Logistic regression analysis revealed an inverse correlation between stress rate of the front-posterior and bottom wall and left ventricle systolic wall strength. In contrast, a positive correlation was found between the mean velocity of circumferential fibre shortening (mVCF) or heart rate-adjusted mVCF (RVCF) and WSsc. Using regression equations, predicted values for mVCF and RVCF in animals with sepsis were significantly higher than measured values at 4- 5- and 6-h time-points.ConclusionsThese findings will further the understanding of pathophysiological alterations in SIMD at the early stage of sepsis, and suggest that strain rate may reflect the nature of myocardial contractility.