Short-chain fatty acids (SCFAs) with the anti-inflammatory capacity are produced by intestinal bacteria; however, their effect on the acute systematical inflammation remains unclear. This study aimed to investigate the effects of SCFAs, acetate, propionate and butyrate, on septic shock and the underlying mechanism. The LPS-induced septic model was used to evaluate the function of SCFAs by survival rate observation. Only butyrate, but not acetate or propionate, significantly decrease the mortality of septic mice. At 2 h and 6 h of LPS administration, the levels of TNF-α, IL-6 and IL-1β in plasma were measured by ELISA to estimate the effects of butyrate pretreatment on excessive inflammation. And the anti-inflammatory mediators including TGF-β, IL-10 and LXT4 in plasma were detected for further mechanism study in septic mice. Moreover, the murine macrophage-like RAW 264.7 cells were stimulated by LPS to further confirm the finding in vivo. Pretreatment with butyrate led to significant attenuation of the LPS-induced elevation of TNF-α, IL-6 and IL-1β levels. However, when detecting the anti-inflammatory factors, a significant increase in IL-10, but not TGF-β or LXT4, was shown in butyrate-pretreated group. Pretreatment of RAW 264.7 cells with butyrate led to downregulation of LPS-induced pro-inflammatory mediators, IL-6 and IL-1β, but did not affect the level of TNF-α, and increased IL-10 (P < 0.01). In conclusion, SCFA butyrate significantly attenuated the inflammation against sepsis through upregulation of anti-inflammatory IL-10.
Dexmedetomidine (DMED), an alpha-2 adrenoreceptor agonist, has been widely used in regional anesthesia procedures. However, the effect of DMED on local anesthetic cardiotoxicity has not been well delineated. This study consisted of two experiments. In experiment A, 42 Sprague–Dawley (SD) rats were randomly divided into 6 groups ( n = 7), each group was pretreated with DMED 0 μg kg−1 (D0 group), 1 μg kg−1 (D1 group), 3 μg kg−1 (D3 group), 6 μg kg−1 (D6 group), 12 μg kg−1 (D12 group), and 24 μg kg−1 (D24 group), administered through the right femoral vein. In experiment B, 20 SD rats were randomly divided into 4 groups ( n = 5), such as control group, DMED group, yohimbine (YOH) group, and DMED + YOH group. Each subgroup in experiment B was also pretreated similarly as in experiment A. After pretreatment of rats as described above (in experiments A and B), bupivacaine 2.5 mg kg−1 min−1 was infused to induce cardiac arrest. In experiment A, the lethal dose threshold of bupivacaine and plasma bupivacaine concentration in D3 and D6 group were higher than the other groups. In experiment B, there was no interaction between DMED and YOH in lethal dose threshold, arrhythmia time, plasma concentration of bupivacaine, and myocardial content of bupivacaine. DMED doses of 3–6 μg kg−1 elevated the lethal dose threshold of bupivacaine without involvement of the alpha-2 adrenoceptors.
Background: Ultrasound is widely used in critical care for fluid resuscitation in critically ill patients. We conducted a systematic review to assess the relationship between ultrasound-guided fluid resuscitation strategies and usual care in septic shock.Methods: We searched PubMed, Embase, Cochrane Library, Web of Science, and registers for randomized controlled trials to evaluate the prognosis of ultrasound-guided fluid resuscitation in patients with septic shock.Results: Twelve randomized controlled studies with 947 participants were included. Ultrasound-guided fluid resuscitation in patients with septic shock was associated with reduced mortality (risk ratio: 0.78; 95% confidence interval [CI]: 0.65 to 0.94; P = 0.007) and 24-hour fluid volume (mean differences [MD]: −1.02; 95% CI: −1.28 to −0.75; P < 0.001), low heterogeneity (I 2 = 29%, I 2 = 0%), and increased dose of norepinephrine (MD: 0.07; 95% CI: 0.02-0.11; P = 0.002) and dobutamine dose (MD: 2.2; 95% CI: 0.35-4.04; P = 0.02), with low heterogeneity (I 2 = 45%, I 2 = 0%). There was no reduction in the risk of dobutamine use (risk ratio: 1.67; 95% CI: 0.52 to 5.36; P = 0.39; I 2 = 0%). Inferior vena cava-related measures reduced the length of hospital stay (MD: −2.91; 95% CI: −5.2 to −0.62; P = 0.01; low heterogeneity, I 2 = 8%) and length of intensive care unit stay (MD: −2.77; 95% CI: −4.51 to −1.02; P = 0.002; low heterogeneity, I 2 = 0%). The use of the passive leg-raising test combined with echocardiography to assess fluid reactivity was superior. Ultrasound-guided fluid resuscitation did not significantly change the length of the free intensive care unit stay (MD: 1.5; 95% CI: −3.81 to 6.81; P = 0.58; I 2 = 0%).Conclusion: Ultrasound-guided fluid resuscitation in patients with septic shock is beneficial, especially when using inferior vena cavarelated measures and the passive leg-raising test combined with echocardiography.
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