[Stress hyperglycemia and nutritional therapy].

Stress induced hyperglycemia is the body's protect response against strong (patho-physiological and/or psychological) stress, sometimes the blood glucose level is too high due to out of the body's adjustment. Renal glucose threshold (about 9 mmol/L) is a window of glucose leak from capillary to interstitial tissue. It is important to keep blood glucose level < 9 mmol/L, for reducing vascular sclerosis as well as organs hypoperfusion, meanwhile pay attention to preventing more dangerous hypoglycemia. Glucose, as the main energy substrate, should be daily supply and its metabolism should be monitored. We used to talk "nutritional support". Support is conform the physiological ability of host, but therapy is to coordinate and change pathophysiology. So, nutritional support is not equal to nutritional therapy. For critical ill patients, we need to emphasize "nutritional therapy", i.e, do not give nutritional treatment without metabolic monitoring, make up for deficiencies and avoid metabolites overloading, rational adjustment to protect and coordinate organs function.

Xuebijing Administration Alleviates Pulmonary Endothelial Inflammation and Coagulation Dysregulation in the Early Phase of Sepsis in Rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Xuebijing injection is a Chinese herbal-derived drug composed of radix paeoniaerubra, rhizomachuanxiong, Salvia miltiorrhiza, floscarthami, and Angelica sinensis. This study aimed to investigate the effects of Xuebijing administration on pulmonary endothelial injury and coagulation dysfunction in a cecal ligation and puncture (CLP)-induced sepsis rat model. MATERIALS AND METHODS: A CLP-induced sepsis rat model was established. The CLP rats were treated with a vehicle or Xuebijing via intravenous infusion and sacrificed at 2, 4, 6, 8, or 12 h after CLP for lung tissue and blood sample collection. The mean arterial pressure (MAP) was monitored. Transmission microscopy examination and H&E staining were performed to observe pulmonary structural alterations. Enzyme linked immunosorbent assay (ELISA) was performed to measure the plasma levels of epithelial markers, proinflammatory cytokines, and coagulation-related proteins. RESULTS: Compared with vehicle treatment, Xuebijing administration maintained the MAP in the normal range until 11 h after CLP. Transmission microscopy and H&E staining revealed that Xuebijing administration alleviated alveolar-capillary barrier impairments and lung inflammation in CLP rats. ELISA showed that Xuebijing administration effectively reversed CLP-induced elevations in the plasma levels of epithelial markers endothelin-1 and von Willebrand factor, starting 6 and 8 h after CLP, respectively. Xuebijing administration also significantly abolished CLP-induced rises in circulating proinflammatory cytokines interleukin 6 (IL-6) at 6 h after CLP, IL-1ß at 2 and 12 h after CLP, and TNF-α at 2, 4, 6, 8, and 12 h after CLP. In addition, Xuebijing administration strongly reversed CLP-induced alterations in circulating active protein C and tissue-type plasminogen activator, starting 4 h and 2 h after CLP, respectively. CONCLUSIONS: Xuebijing ameliorates pulmonary endothelial injury, systemic inflammation, and coagulation dysfunction in early sepsis.

The Positive and Negative Effects of Calcium Supplementation on Mortality in Septic ICU Patients Depend on Disease Severity: A Retrospective Study from the MIMIC-III.

Background: Calcium administration in septic patients with hypocalcemia is a controversial issue. The present study preliminarily investigated the effects of calcium supplementation on the length of hospitalization and mortality in septic ICU patients with different severities of hypocalcemia and disease. Method: A total of 5761 eligible septic patients, including 2689 who received calcium supplementation and 3072 who did not receive calcium supplementation, were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The cofounding covariates between the calcium supplement and nonsupplement groups were balanced using the propensity score matching model. We compared the length of stay (LOS) in the ICU and hospital with 28-day and hospital mortality and stratified the analysis according to the sequential organ failure assessment (SOFA) score and ionized calcium (iCa) at the first ICU admission in the matched groups. Results: The results showed that iCa at the first ICU admission was associated with mortality in sepsis patients (HR: 0.421; 95% CI: 0.211∼0.837), but the lowest mortality rate was observed in patients with mild hypocalcemia. A total of 993 paired patients were included in the analysis after propensity score matching. Regardless of the SOFA score or presence of iCa, the LOS in the ICU was higher in the calcium supplement group than in the nonsupplement group. The survival analysis was stratified by the SOFA score and showed that calcium supplementation reduced mortality when the patient's SOFA score was ≥8 (p=0.002), and it worsened the outcome when the patient's SOFA score was ≤4 (p=0.010). It had no significant effect on patients with SOFA scores ranging from 5 to 7 (p=0.911). Conclusion: Our results showed that mild hypocalcemia may be protective in septic patients, and calcium supplementation may have positive and negative effects on mortality depending on disease severity. The SOFA score may be a valuable clinical index for decisions regarding calcium administration.

Hypocalcemia in sepsis: analysis of the subcellular distribution of Ca2+ in septic rats and LPS/TNF-α-treated HUVECs.

INTRODUCTION: Hypocalcemia has been widely recognized in sepsis patients. However, the cause of hypocalcemia in sepsis is still not clear, and little is known about the subcellular distribution of Ca2+ in tissues during sepsis. METHODOLOGY: We measured the dynamic change in Ca2+ levels in body fluid and subcellular compartments, including the cytosol, endoplasmic reticulum and mitochondria, in major organs of cecal ligation and puncture (CLP)-operated rats, as well as the subcellular Ca2+ flux in HUVECs which treated by endotoxin and cytokines. RESULTS: In the model of CLP-induced sepsis, the blood and urinary Ca2+ concentrations decreased rapidly, while the Ca2+ concentration in ascites fluid increased. The Ca2+ concentrations in the cytosol, ER, and mitochondria were elevated nearly synchronously in major organs in our sepsis model. Moreover, the calcium overload in CLP-operated rats treated with calcium supplementation was more severe than that in the non-calcium-supplemented rats but was alleviated by treatment with the calcium channel blocker verapamil. Similar subcellular Ca2+ flux was found in vitro in HUVECs and was triggered by lipopolysaccharide (LPS)/TNF-α. CONCLUSIONS: Ca2+ influx from the blood into the intercellular space and Ca2+ release into ascites fluid may cause hypocalcemia in sepsis and that this process may be due to the synergistic effect of endotoxin and cytokines.