Chai Wz

Acute renal failure during sepsis: potential role of cell cycle regulation.

OBJECTIVES This study aimed to evaluate cell cycle regulation in acute kidney injury after intraperitoneal sepsis in rats. METHODS Polymicrobial sepsis was induced by cecal ligation and puncture (CLP) in rats. At 0, 6, 12, 24, 48, and 72 h after CLP, serum creatinine was evaluated. DNA content of isolated kidney cells was analyzed using flow cytometer. Furthermore, the expression of p21, p53, cyclin D1, cyclin E, CDK2, CDK4 and P-pRb was also measured by western blot. RESULTS After sepsis-induced by CLP, kidney injury of rat was associated with G1 cell cycle arrest, however, recovery of renal function related to cell cycle progression 48h after CLP. Results also showed that the upregulation of p53 and p21 was correlated with G1 cell arrest in 48h after CLP. Nevertheless, upregulation of cyclin D1/CDK4 and cyclin E/CDK2 induced pRb phosphorylation, which resulted in the G1/S transition 48 h after CLP. CONCLUSION The data suggest that G1 cell cycle arrest may play a role in the initiation of kidney injury, whereas, through regulating cell cycle, p53, p21, CDKs, cyclins and P-pRb may be involved in the injury or recovery of renal function after intraperitoneal sepsis.

Melatonin improved rat cardiac mitochondria and survival rate in septic heart injury

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.

Combining central venous-to-arterial partial pressure of carbon dioxide difference and central venous oxygen saturation to guide resuscitation in septic shock

PURPOSE Central venous oxygen saturation (Scvo2) is a useful therapeutic target when treating septic shock. We hypothesized that combining Scvo2 and central venous-to-arterial partial pressure of carbon dioxide difference (△Pco2) may provide additional information about survival. MATERIALS AND METHODS We performed a retrospective analysis of 172 patients treated for septic shock. All patients were treated using goal-directed therapy to achieve Scvo2 ≥ 70%. After 6 hours of treatment, we divided patients into 4 groups based on Scvo2 (<70% or ≥ 70%) and △Pco2 (<6 mm Hg or ≥ 6 mm Hg). RESULTS Overall, 28-day mortality was 35.5%. For patients in whom the Scvo2 target was not achieved at 6 hours, mortality was 50.0%, compared with 29.5% in those in whom Scvo2 exceeded 70% (P = .009). In patients with Scvo2 ≥ 70%, mortality was lower if △Pco2 was <6 mm Hg than if △Pco2 was ≥ 6 mm Hg (56.1% vs 16.1%, respectively; P < .001) and 6-hour lactate clearance was superior (0.01 ± 0.61 vs 0.21 ± 0.31, respectively; P = .016). CONCLUSIONS The combination of Scvo2 and △Pco2 appears to predict outcome in critically ill patients resuscitated from septic shock better than Scvo2 alone. Patients who meet both targets appear to clear lactate more efficiently.

Integrated Cardiopulmonary Sonography A Useful Tool for Assessment of Acute Pulmonary Edema in the Intensive Care Unit

Bedside sonography has become a popular method of assessment of critically ill patients with shock and dyspnea. This study evaluated the usefulness of integrated cardiopulmonary sonography for assessment of acute pulmonary edema.

Role of sTREM-1 in predicting mortality of infection: a systematic review and meta-analysis

Objectives Several studies have investigated the prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with infection. However, the result was controversial. Thus, the purpose of the present meta-analysis was to determine the prognostic value of the sTREM-1 level in predicting mortality at the initial stage of infection. Methods The literature was searched in the PubMed, EMBASE, Web of Knowledge and Cochrane databases. A 2×2 contingency table was constructed on the basis of mortality and sTREM-1 levels in patients with infection. 2 authors independently judged study eligibility and extracted data. The prognostic value of sTREM-1 in predicting mortality was determined using a bivariate meta-analysis model. Q-test and I2 index were used to test heterogeneity. Results 9 studies were selected from 803 studies. An elevated sTREM-1 level was associated with a higher risk of death in infection, with pooled risk ratio (RR) was 2.54 (95% CI 1.77 to 3.65) using a random-effects model (I2=53.8%). With the bivariate random-effects regression model, the pooled sensitivity and specificity of sTREM-1 to predict mortality in infection were 0.75 (95% CI 0.61 to 0.86) and 0.66 (95% CI 0.54 to 0.75), respectively. The diagnostic OR was 6 (95% CI 3 to 10). The overall area under the summary receiver operator characteristic (SROC) curve was 0.76 (95% CI 0.72 to 0.79). When we calculated the sepsis subgroup, the pooled RR was 2.98 (95% CI 2.19 to 4.40). The pooled sensitivity and specificity were 0.74 (95% CI 0.58 to 0.85) and 0.72 (95% CI 0.62 to 0.80), respectively. The overall area under the SROC curve was 0.78 (95% CI 0.74 to 0.81). Conclusions Elevated sTREM-1 concentrations had a moderate prognostic significance in assessing the mortality of infection in adult patients. However, sTREM-1 alone is insufficient to predict mortality as a biomarker.

The transcutaneous oxygen challenge test: a noninvasive method for detecting low cardiac output in septic patients.

ABSTRACT The transcutaneous partial pressure of oxygen (PtcO2) index has been used to detect low-flow state in circulatory failure, but the value of the transcutaneous oxygen challenge test (OCT) to estimate low cardiac output has not been thoroughly evaluated. The prospective observational study examined 62 septic patients requiring PiCCO-Plus for cardiac output monitoring. Simultaneous basal blood gases from the arterial, central venous catheters were obtained. Cardiac indices were measured by the transpulmonary thermodilution technique at the same time, then the 10-min inspired 1.0 fractional inspired oxygen concentration (FIO2) defined as the OCT was performed. Transcutaneous partial pressure of oxygen was measured continuously by using a noninvasive transcutaneous monitor throughout the test. The values for arterial pressure of oxygen (PaO2) were examined on inspired of 1.0 FIO2. We calculated the PtcO2 index = (baseline PtcO2/baseline PaO2), 10-min OCT (10 OCT) = (PtcO2 after 10 min on inspired 1.0 O2) − (baseline PtcO2), and the oxygen challenge index = (10 OCT) / (PaO2 on inspired 1.0 O2 − baseline PaO2). Patients were divided into two groups: a normal cardiac index (CI) group with CI of greater than 3 L/min per m2 (n = 41) and a low CI group with CI of 3 L/min per m2 or less (n = 21). The 10 OCT and the oxygen challenge index predicted a low CI (⩽3 L/min per m2) with an accuracy that was similar to central venous oxygen saturation, which was significantly better than the PtcO2 index. For a 10 OCT value of 53 mmHg, sensitivity was 0.83; specificity, 0.86; a positive predictive value, 0.92; and a negative predictive value, 0.72 for detecting CI of 3 L/min per m2 or less. We propose that the OCT substituted for the PtcO2 index as an accurate alternative method of PtcO2 for revealing low CI in septic patients.

Using Critical Care Chest Ultrasonic Examination in Emergency Consultation: A Pilot Study

The purpose of this study was to investigate the effects of critical care chest ultrasonic examination (CCUE) by intensivist on the diagnosis and treatment decisions in emergent consultation for patients who may have a problem-need transfer to an intensive care unit (ICU). A total of 130 patients who required emergent consultation in the ordinary wards were included in this study. Patients were randomly divided into conventional group (n = 63) and CCUE group (n = 67, added CCUE). The two groups showed no significant differences in general clinical information or final diagnosis (p > 0.05). The CCUE group had a shorter time to preliminary diagnosis, final diagnosis, treatment response and X-ray/computed tomography examination; a delay in ICU transfer and ICU stay days (3.9 ± 1.2 vs. 5.4 ± 1.9 d, p < 0.05) and a higher diagnostic accuracy than the conventional group (p < 0.001). In conclusion, CCUE could help early diagnosis and therapy for the patient who may need to transfer to the ICU and reduce the ICU stay for in-hospital patients in emergent consultation.

The Role of Uncoupling Protein 2 During Myocardial Dysfunction in a Canine Model of Endotoxin Shock.

ABSTRACT To explore the role of uncoupling protein 2 (UCP2) during myocardial dysfunction in a canine model of endotoxin shock, 26 mongrel canines were randomly divided into the following four groups: A (control group; n = 6), B2 (shock after 2 h; n = 7), B4 (shock after 4 h; n = 7), and B6 (shock after 6 h; n = 6). Escherichia coli endotoxin was injected into the canines via the central vein, and hemodynamics were monitored. Energy metabolism, UCP2 mRNA and protein expression, and UCP2 localization were analyzed, and the correlation between energy metabolism changes, and UCP2 expression was determined. After the canine endotoxin shock model was successfully established, the expression of UCP2 mRNA and protein was found to increase, with later time points showing significant increases (P < 0.05). Immunofluorescence assays of UCP2 in heart tissue showed that UCP2 was localized in the cytoplasm, and its expression pattern was the same as that found in the mRNA and protein analyses. The energy metabolism results revealed that the ADP levels increased, but the ATP and phosphocreatine (PCr) levels and ATP/ADP and PCr/ATP ratios decreased in the model. In particular, the PCr/ATP ratio was significantly different from that of the control group 6 h after shock (P < 0.05). Furthermore, correlation analysis showed that the UCP2 protein and mRNA levels were negatively correlated with myocardial energy levels. In summary, decreased energy synthesis can occur in the myocardium during endotoxin shock, and UCP2 may play an important role in this process. The negative correlation between UCP2 expression and energy metabolism requires further study, as the results might contribute to the treatment of sepsis with heart failure.

Prognostic value of extravascular lung water and its potential role in guiding fluid therapy in septic shock after initial resuscitation.

PURPOSES To explore whether extravascular lung water (EVLW) provides a valuable prognostic tool guiding fluid therapy in septic shock patients after initial resuscitation. MATERIALS AND METHODS We performed a retrospective study of septic shock patients who achieved adequate initial fluid resuscitation with extended hemodynamic monitoring, analyzing the prognostic value of EVLW and whether fluid therapy for 24 (T24) or 24-48 hours (T24-48) after initial resuscitation with a recommended value of EVLW yielded a 28-day mortality advantage. RESULTS One hundred five patients with septic shock were included in this study, 60 (57.1%) of whom died after 28 days. For 48 hours after initial resuscitation, the daily fluid balance (DFB; T24: 2494 ± 1091 vs 1965 ± 964 mL [P = .011] and T24-48: 2127 ± 783 vs 1588 ± 665 mL [P < .001]) and daily maximum values of the EVLW index (EVLWImax; T24: 13.9 ± 3.7 vs 11.5 ± 3.2 mL/kg [P < .001] and T24-48: 14.4 ± 5.3 vs 12.0 ± 4.4 mL/kg [P < .001]) were significantly higher in nonsurvivors than in survivors. In multivariate regression analysis, the DFB (T24: odds ratio [OR] 1.001 [P = .016] and T24-48: OR 1.001 [P = .008]), EVLWImax (T24: OR 2.158 [P = .002] and T24-48: OR 3.277 [P = .001]), blood lactate (T24: OR 1.368 [P = .021] and T24-48: OR 4.112 [P < .001]), and central venous blood oxygen saturation (T24: OR 0.893 [P = .013] and T24-48: OR 0.780 [P = .004]) were all independently associated with the 28-day mortality. A receiver operating characteristic analysis revealed that area under the curve values of 0.82 (95% confidence interval, 0.74-0.91; P < .001) and 0.90 (95% confidence interval, 0.83-0.96; P < .001) for EVLWImax ≥ 12.5 mL/kg (T24 and T24-48) predicted a 28-day mortality with sensitivities of 88% (80%-96%) and 95% (90%-100%) and specificities of 60% (46%-74%) and 76% (63%-89%).The EVLWImax was correlated with DFB with Spearman ρ values of 0.497 (T24: P < .001) and 0.650 (T24-48: P < .001). Cox survival and regression analyses demonstrated that EVLWImax ≥ 12.5 mL/kg (T24 and T24-48) was associated with higher risk and increased mortality, with adjusted ORs of 4.77 (P < .001) and 10.86 (P < .001). CONCLUSIONS A higher EVLW in septic shock patients after initial resuscitation was associated with a more positive fluid balance and increased mortality, which is an independent predictor of the 28-day mortality in septic shock patients after initial resuscitation.

Elevated Mean Airway Pressure and Central Venous Pressure in the First Day of Mechanical Ventilation Indicated Poor Outcome

Objectives: The relationship between respiratory mechanical parameters and hemodynamic variables remains unclear. This study was performed to determine whether mean airway pressure and central venous pressure in the first day of mechanical ventilation are associated with patient outcomes. Design: Retrospective first 24-hour comparison during ICU stay. Setting: The Department of Critical Care Medicine of Peking Union Medical College Hospital. Patients: Patients with mechanical ventilation. Interventions: None. Measurements and Main Results: The clinical data of patients who received mechanical ventilation, especially respiratory and hemodynamic data, were collected and analyzed. In terms of the hemodynamic and perfusion data, the nonsurvivors group (177/2,208) had higher heart rate, respiratory rate, central venous pressure, and lactates and a lower perfusion index and P(v-a)CO2 (p < 0.05). In terms of respiratory condition, mean airway pressure, peak airway pressure, positive end-expiratory pressure, driving pressure, and inspiratory time/total respiration time of nonsurvivors were significantly higher, and arterial oxygen pressure and dynamic compliance worsened and were lower than the survivors (p < 0.05). Increased central venous pressure (odds ratio, 1.125; 95% CI, 1.069–1.184; p < 0.001) and elevated mean airway pressure (odds ratio, 1.125; 95% CI, 1.069–1.184; p < 0.001) were independently associated with 28-day mortality. The area under receiver operating characteristic demonstrated that central venous pressure and mean airway pressure were measured at 0.795 (95% CI, 0.654–0.757) and 0.833 (95% CI, 0.608–0.699), respectively. Based on the cutoff of central venous pressure and mean airway pressure, all of the participants were divided into the following groups: low central venous pressure and mean airway pressure, only high central venous pressure or mean airway pressure, or high central venous pressure and mean airway pressure. Post hoc tests showed significant differences among these three groups based on 28-day survival (log rank [Mantel-Cox], 131.931; p < 0.001). Conclusions: During the first 24 hours of mechanical ventilation, patients with elevated mean airway pressure and elevated central venous pressure had worse outcomes.