[Research progress of multidisciplinary team co-management models for geriatric hip fracture treatment].

OBJECTIVE: To summarize the research progress of multidisciplinary team (MDT) co-management models in the clinical treatment of geriatric hip fractures. METHODS: The literature about types and characteristics of MDT for geriatric hip fracture treatment were extensively reviewed, and the advantages of its clinical application were analysed and summarised. Finally, the MDT model and characteristics of geriatric hip fracture in the Zhongda Hospital affiliated to Southeast University were introduced in detail. RESULTS: Clinical models of MDT are diverse and have their own characteristics, and MDT can shorten the length of stay and waiting time before operation, reduce the incidence of internal complications, save labor costs, and reduce patient mortality. CONCLUSION: The application of MDT in the treatment of geriatric hip fracture has achieved remarkable results, which provides an optimal scheme for the treatment of geriatric hip fracture.

High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care.

Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding XueBiJing, a five-herb medicine, to antibiotic-based sepsis care. Although adding XueBiJing further reduced 28-day mortality via modulating the host response, pharmacokinetic herb-drug interaction is a widely recognized issue that needs to be studied. Building on our earlier systematic chemical and human pharmacokinetic investigations of XueBiJing, we evaluated the degree of pharmacokinetic compatibility for XueBiJing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both XueBiJing‒antibiotic and antibiotic‒XueBiJing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study XueBiJing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no XueBiJing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could, due to their inhibition of uridine 5'-diphosphoglucuronosyltransferase 2B15, organic anion transporters 1/2 and/or organic anion-transporting polypeptide 1B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions (resulting in increased exposure) are likely desirable due to these XueBiJing compounds' low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from XueBiJing. Collectively, XueBiJing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations.

[Clinical application of multidisciplinary team co-management in geriatric hip fractures].

OBJECTIVE: To observe the clinical application of multidisciplinary team (MDT) treatment in the management of geriatric hip fractures and evaluate its effectiveness. METHODS: The clinical data of 76 elderly patients with hip fracture managed by MDT approach between August 2016 and February 2018 (MDT group) were retrospectively analyzed and compared with 102 patients managed by traditional orthopedics approach between January 2014 and December 2015 (conventional group). There was no significant difference in gender, age, fracture type, surgical procedure, and other general data between the two groups ( P>0.05). However, the number of comorbidities in the MDT group was significantly higher than that in the conventional group ( t=6.295, P=0.000), and the proportion of the number of comorbidities between the two groups was also significantly different ( χ 2=28.442, P=0.000). The consultation rate and transfer rate, time to surgery, rate of surgery within 2 or 3 days, operation time, postoperative hospitalization stay, length of hospitalization stay, hospitalization expense, rate of loss to follow-up, and mortality during hospitalization, 30-day mortality, 90-day mortality, and 1-year mortality after operation were compared between the two groups. RESULTS: The rates of total consultations of the conventional group and the MDT group were 56.86% (58/102) and 56.58% (43/76), respectively, and the rates of total transferred patients were 15.69% (16/102) and 15.79% (12/76), respectively, with no significant differences ( P>0.05). Among them, the proportion of patients who transferred into intensive care unit (ICU) in conventional group was significantly higher than that in MDT group and the rates of patients who received geriatric consultation or transferred into geriatric department in MDT group were both significantly higher than those in conventional group ( P<0.05). There was no significant difference in rates of other department consultation or transfer between the two groups ( P>0.05). The time to surgery, operation time, postoperative hospitalization stay, and length of hospitalization stay in MDT group were significantly less than those in conventional group, but the proportion of patients who received surgery within 3 days in MDT group was significantly higher than that in conventional group ( P<0.05). There was no significant difference in the proportion of patients who received surgery within 2 days ( χ 2=2.027, P=0.155). The hospitalization expenses of total patients, femoral neck fracture, and intertrochanteric fracture subgroups in MDT group were all significantly higher than those in conventional group ( P<0.05). However, there was no significant difference in hospitalization expense of subtrochanteric fracture subgroup between the two groups ( Z=-1.715, P=0.086). The rate of loss to follow-up in conventional group and MDT group was 6.86% (7/102) and 3.95% (3/76), respectively, with no significant difference ( χ 2=0.698, P=0.403). The mortalities at hospitalization, 1 month, 3 months, and 1 year after operation in conventional group were 0, 1.05% (1/95), 3.16% (3/95), and 7.37% (7/95), respectively, and in MDT group were 0, 0, 2.74% (2/73), 6.85% (5/73), respectively, showing no significant differences in mortalities between the two groups ( P>0.05). CONCLUSION: MDT model in the management of geriatric hip fractures has been shown to reduce time to surgery, postoperative hospitalization stay, length of hospitalization stay, operation time, and the proportion of patients who received ICU consultation or transferred into ICU. Furthermore, MDT can improve the capacity for developing operations for patients with complex medical conditions and make medical resources used more rationally.

Genetic Modification of Mesenchymal Stem Cells Overexpressing Angiotensin II Type 2 Receptor Increases Cell Migration to Injured Lung in LPS-Induced Acute Lung Injury Mice.

Although mesenchymal stem cells (MSCs) transplantation has been shown to promote the lung respiration in acute lung injury (ALI) in vivo, its overall restorative capacity appears to be restricted mainly because of low retention in the injured lung. Angiotensin II (Ang II) are upregulated in the injured lung. Our previous study showed that Ang II increased MSCs migration via Ang II type 2 receptor (AT2R). To determine the effect of AT2R in MSCs on their cell migration after systemic injection in ALI mice, a human AT2R expressing lentiviral vector and a lentivirus vector carrying AT2R shRNA were constructed and introduced into human bone marrow MSCs. A mouse model of lipopolysaccharide-induced ALI was used to investigate the migration of AT2R-regulated MSCs and the therapeutic potential in vivo. Overexpression of AT2R dramatically increased Ang II-enhanced human bone marrow MSC migration in vitro. Moreover, MSC-AT2R accumulated in the damaged lung tissue at significantly higher levels than control MSCs 24 and 72 hours after systematic MSC transplantation in ALI mice. Furthermore, MSC-AT2R-injected ALI mice exhibited a significant reduction of pulmonary vascular permeability and improved the lung histopathology and had additional anti-inflammatory effects. In contrast, there were less lung retention in MSC-ShAT2R-injected ALI mice compared with MSC-Shcontrol after transplantation. Thus, MSC-ShAT2R-injected group exhibited a significant increase of pulmonary vascular permeability and resulted in a deteriorative lung inflammation. Our results demonstrate that overexpression of AT2R enhance the migration of MSCs in ALI mice and may provide a new therapeutic strategy for ALI. Stem Cells Translational Medicine 2018;7:721-730.

Predictive utilities of neutrophil gelatinase-associated lipocalin (NGAL) in severe sepsis.

BACKGROUND: We aim to investigate the predictive value of plasma neutrophil gelatinase-associated lipocalin (pNGAL) in patients with severe sepsis. METHODS: A total of 124 patients were enrolled in this observational study. Blood samples were obtained at admission, on day 2 and day 7. Receiver operating characteristic (ROC) curves were generated to assess the utility of pNGAL in prediction of 28-day mortality and need for CRRT. Cox regression curves were built with and without pNGAL for 28-day mortality prediction to determine NGAL's contributive predictive value. RESULTS: Plasma NGAL was significantly increased in non-survivors group on day 2 and 7 and predicted 28-day mortality with AuROC values of 0.675 (95% CI 0.570-0.780) and 0.752 (95% CI 0.619-0.885). Addition of day 2 NGAL to the clinical model resulted in a net reclassification index (NRI) increment of 0.40 (95% CI 0.06-0.75, P = 0.028) for prediction of 28-day mortality. The AuROC of NGAL at admission and day 2 was greater than creatinine in prediction of the need for CRRT. CONCLUSION: Plasma NGAL discriminated 28-day survivors from non-survivors on day 2 and 7 and was a relatively robust predictor of 28-day mortality prediction. Plasma NGAL possibly outperformed creatinine in the prediction of need for CRRT.

Chemokine receptor 7 overexpression promotes mesenchymal stem cell migration and proliferation via secreting Chemokine ligand 12.

Great interest has been shown in mesenchymal stem cell (MSC) therapy in a wide variety of clinical domains. However, the therapeutic efficiency depends on the proliferation and migration of MSCs. Chemokine receptors are involved in regulating the proliferation and migration to the specific organs of MSCs in different microenvironments. CXC receptor seven (CXCR7), a newly discovered Chemokine ligand 12 (CXCL12) receptor, has organ specificity for tumour migration. We hypothesized that CXCR7 expression affects proliferation and migration of MSCs. In present study, we constructed long-term and stable mMSCs lines overexpressing and suppressing CXCR7 modifications with lentiviral vectors. The transduction efficiencies, mRNA and protein expression of CXCR7 were significantly regulated. CXCR7 gene overexpression promoted mMSCs proliferation and migration, whereas suppressing CXCR7 had the opposite effect. Additional CXCL12 improved the vertical migration of mMSCs. The overexpression of CXCR7 increased the MSC-secreted CXCL12, VCAM-1, CD44 and MMP2 levels, which contributed to the improvement of mMSC proliferation and migration. Therefore, overexpressing CXCR7 improved the proliferation and migration of mMSCs, which may be attributable to the CXCL12 secreted by MSCs, leading to a positive feedback loop for CXCL12/CXCR7 axis. Our results may provide a potential method for improving the treatment effectiveness of mMSCs by overexpressing CXCR7.

Effect of Remote Ischemic Preconditioning on Outcomes in Adult Cardiac Surgery: A Systematic Review and Meta-analysis of Randomized Controlled Studies.

BACKGROUND: Remote ischemic preconditioning (RIPC) has been demonstrated to prevent organ dysfunction in cardiac surgery patients. However, recent large, prospective, multicenter, randomized controlled trials (RCTs) had controversial results. Thus, a meta-analysis of RCTs was performed to investigate whether RIPC can reduce the incidence of acute myocardial infarction (AMI), acute kidney injury (AKI), and mortality in adult cardiac surgery patients. METHODS: Study data were collected from Medline, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. RCTs involving the effect of RIPC on organ protection in cardiac surgery patients, which reported the concentration or total release of creatine kinase-myocardial band, troponin I/troponin T (TNI/TNT) after operation, or the incidence of AMI, AKI, or mortality, were selected. Two reviewers independently extracted data using a standardized data extraction protocol where TNI or TNT concentrations; total TNI released after cardiac surgery; and the incidence of AKI, AMI, and mortality were recorded. Review Manager 5.3 software was used to analyze the data. RESULTS: Thirty trials, including 7036 patients were included in the analyses. RIPC significantly decreased the concentration of TNI/TNT (standard mean difference [SMD], -0.25 ng/mL; 95% confidence interval [CI], -0.41 to -0.048 ng/mL; P = .004), creatine kinase-myocardial band (SMD, -0.22; 95% CI, -0.07-0.35 ng/mL; P = .46), and the total TNI/TNT release (SMD, -0.49 ng/mL; 95% CI, -0.93 to -0.55 ng/mL; P = .03) in cardiac surgery patients after a procedure. However, RIPC could not reduce the incidence of AMI (relative risk, 0.89; 95% CI, 0.70-1.13; P = .34) and AKI (relative risk, 0.88; 95% CI, 0.72-1.06; P = .18), and there was also no effect of RIPC on mortality in adult cardiac surgery patients. Interestingly, subgroup analysis showed that RIPC reduced incidence of AKI and mortality of cardiac surgery patients who received volatile agent anesthesia. CONCLUSIONS: Our meta-analysis demonstrated that RIPC reduced TNI/TNT release after cardiac surgery. RIPC did not significantly reduce the incidence of AKI, AMI, and mortality. However, RIPC could reduce mortality in patients receiving volatile inhalational agent anesthesia.

The effects of low tidal ventilation on lung strain correlate with respiratory system compliance.

BACKGROUND: The effect of alterations in tidal volume on mortality of acute respiratory distress syndrome (ARDS) is determined by respiratory system compliance. We aimed to investigate the effects of different tidal volumes on lung strain in ARDS patients who had various levels of respiratory system compliance. METHODS: Nineteen patients were divided into high (Chigh group) and low (Clow group) respiratory system compliance groups based on their respiratory system compliance values. We defined compliance ≥0.6 ml/(cmH2O/kg) as Chigh and compliance <0.6 ml/(cmH2O/kg) as Clow. End-expiratory lung volumes (EELV) at various tidal volumes were measured by nitrogen wash-in/washout. Lung strain was calculated as the ratio between tidal volume and EELV. The primary outcome was that lung strain is a function of tidal volume in patients with various levels of respiratory system compliance. RESULTS: The mean baseline EELV, strain and respiratory system compliance values were 1873 ml, 0.31 and 0.65 ml/(cmH2O/kg), respectively; differences in all of these parameters were statistically significant between the two groups. For all participants, a positive correlation was found between the respiratory system compliance and EELV (R = 0.488, p = 0.034). Driving pressure and strain increased together as the tidal volume increased from 6 ml/kg predicted body weight (PBW) to 12 ml/kg PBW. Compared to the Chigh ARDS patients, the driving pressure was significantly higher in the Clow patients at each tidal volume. Similar effects of lung strain were found for tidal volumes of 6 and 8 ml/kg PBW. The "lung injury" limits for driving pressure and lung strain were much easier to exceed with increases in the tidal volume in Clow patients. CONCLUSIONS: Respiratory system compliance affected the relationships between tidal volume and driving pressure and lung strain in ARDS patients. These results showed that increasing tidal volume induced lung injury more easily in patients with low respiratory system compliance. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01864668 , Registered 21 May 2013.

The Vascular Endothelial Growth Factors-Expressing Character of Mesenchymal Stem Cells Plays a Positive Role in Treatment of Acute Lung Injury In Vivo.

Recently, mesenchymal stem cells (MSC) have been proved to be beneficial in acute respiratory distress syndrome (ARDS). Vascular endothelial growth factor (VEGF) is an important angiogenesis factor that MSC release. However, the precise role of VEGF-expressing character of MSC in the MSC treatment for ARDS remains obscure. Here, we firstly knocked down the gene VEGF in MSC (MSC-ShVEGF) with lentiviral transduction. Then we injected the MSC-ShVEGF to rats with lipopolysaccharide-induced acute lung injury (ALI) via the tail vein. Data showed that MSC transplantation significantly increased VEGF levels in the lung, reduced lung permeability, protected lung endothelium from apoptosis, facilitated VE-cadherin recovery, controlled inflammation, and attenuated lung injury. However, VEGF gene knockdown in MSC led to relatively insufficient VEGF expression in the injured lung and significantly diminished the therapeutic effects of MSC on ALI, suggesting an important role of VEGF-expressing behavior of MSC in the maintenance of VEGF in the lung and the MSC treatment for ALI. Hence, we conclude that MSC restores the lung permeability and attenuates lung injury in rats with ALI in part by maintaining a "sufficient" VEGF level in the lung and the VEGF-expressing character of MSC plays a positive role in the therapeutic effects of MSC on ARDS.

The hepatocyte growth factor-expressing character is required for mesenchymal stem cells to protect the lung injured by lipopolysaccharide in vivo.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a life-threatening condition in critically ill patients. Recently, we have found that mesenchymal stem cells (MSC) improved the permeability of human lung microvascular endothelial cells by secreting hepatocyte growth factor (HGF) in vitro. However, the properties and functions of MSC may change under complex circumstances in vivo. Here, we sought to determine the role of the HGF-expressing character of MSC in the therapeutic effects of MSC on ARDS in vivo. METHODS: MSC with HGF gene knockdown (MSC-ShHGF) were constructed using lentiviral transduction. The HGF mRNA and protein levels in MSC-ShHGF were detected using quantitative real-time polymerase chain reaction and Western blotting analysis, respectively. HGF levels in the MSC culture medium were measured by enzyme-linked immunosorbent assay (ELISA). Rats with ARDS induced by lipopolysaccharide received MSC infusion via the tail vein. After 1, 6, and 24 h, rats were sacrificed. MSC retention in the lung was assessed by immunohistochemical assay. The lung wet weight to body weight ratio (LWW/BW) and Evans blue dye extravasation were obtained to reflect lung permeability. The VE-cadherin was detected with inmmunofluorescence, and the lung endothelial cell apoptosis was assessed by TUNEL assay. The severity of lung injury was evaluated using histopathology. The cytokines and HGF levels in the lung were measured by ELISA. RESULTS: MSC-ShHGF with markedly lower HGF expression were successfully constructed. Treatment with MSC or MSC carrying green fluorescent protein (MSC-GFP) maintained HGF expression at relatively high levels in the lung at 24 h. MSC or MSC-GFP decreased the LWW/BW and the Evans Blue Dye extravasation, protected adherens junction VE-cadherin, and reduced the lung endothelial cell apoptosis. Furthermore, MSC or MSC-GFP reduced the inflammation and alleviated lung injury based on histopathology. However, HGF gene knockdown significantly decreased the HGF levels without any changes in the MSC retention in the lung, and diminished the protective effects of MSC on the injured lung, indicating the therapeutic effects of MSC on ARDS were partly associated with the HGF-expressing character of MSC. CONCLUSIONS: MSC restores lung permeability and lung injury in part by maintaining HGF levels in the lung and the HGF-expressing character is required for MSC to protect the injured lung.

How much esophageal pressure-guided end-expiratory transpulmonary pressure is sufficient to maintain lung recruitment in lavage-induced lung injury?

BACKGROUND: Because of limitations of the esophageal balloon technique, the value of using esophageal pressure (Pes)-guided end-expiratory transpulmonary pressure (PL-exp) to maintain lung recruitment in adult respiratory distress syndrome is controversial. This study aimed to investigate whether tailoring PL-exp to greater than 0 was enough to maintain lung recruitment. METHODS: Ten pigs with severe lavage-induced lung injury were mechanically ventilated in a decremental positive end-expiratory pressure (PEEP) trial that was reduced from 20 to 6 cm H2O after full-lung recruitment. Respiratory mechanics, blood gases, hemodynamic data, and whole-lung computed tomography scans were recorded at each PEEP level. Open-lung PEEP (OL-PEEP) was determined by computed tomography, while Pes-guided PEEP (Pes-PEEP) was to maintain PL-exp greater than 0. RESULTS: OL-PEEP was higher than Pes-PEEP, which induced a higher PL-exp at OL-PEEP than at Pes-PEEP (4.6 [1.6] cm H2O vs. 1.2 [0.6] cm H2O, p < 0.001). Compared with OL-PEEP, the nonaerated lung region was significantly increased at Pes-PEEP. Superimposed pressure (SP) of the lung tissue between the esophageal plane and the dorsal level was higher at Pes-PEEP than at OL-PEEP, whereas PL-exp at the dorsal level was lower at Pes-PEEP than at OL-PEEP (-1.5 [0.7] cm H2O vs. 2.5 [1.5] cm H2O, p < 0.001). The SP correlated with PL-exp at the dorsal level and the nonaerated lung region. CONCLUSION: In this surfactant-depleted model, maintaining PL-exp just greater than 0 using Pes was unable to maintain lung recruitment; this was partly caused by a lack of compensation for the increased SP between the esophageal plane and the dorsal level.

Effects of recruitment maneuvers with PEEP on lung volume distribution in canine models of direct and indirect lung injury.

Lung recruitment maneuvers can help open collapsed lung units for sufficient oxygenation, and positive end expiratory pressure (PEEP) is used to keep the lung open after recruitment. However, the application of high PEEP levels may play a significant role in causing regional lung hyperinflation during mechanical ventilation. The authors sought to study the effects of PEEP targeting optimal oxygenation on regional lung volume distribution in a direct and an indirect acute respiratory distress syndrome (ARDS) model. ARDS was induced by either surfactant depletion or oleic acid injection in dogs. After lung recruitment, PEEP was decreased from 20 to 10 cmH2O in 2 cmH2O steps every 10 min to examine regional lung aeration by using computed tomography. Lung injury appeared to be localized in the model of surfactant depletion while it widely diffused after oleic acid infusion. At PEEP levels that achieved optimal oxygenation, nonaerated lung units decreased and normally aerated lung units enhanced, but hyperinflated areas increased significantly in both models (P < 0.05). Hyperinflated areas were greater in the surfactant depletion model than in the oleic acid model at PEEP levels applied (P < 0.05). Optimal oxygenation guided PEEP may cause hyperinflated in both focal lung injury and diffused lung injury post lung recruitment. Hyperinflation was more susceptible in focal lung injury than in diffused lung injury post lung recruitment.

Higher frequency ventilation attenuates lung injury during high-frequency oscillatory ventilation in sheep models of acute respiratory distress syndrome.

BACKGROUND: High-frequency oscillatory ventilation (HFOV) at higher frequencies minimizes the tidal volume. However, whether increased frequencies during HFOV can reduce ventilator-induced lung injury remains unknown. METHODS: After the induction of acute respiratory distress syndrome in the model by repeated lavages, 24 adult sheep were randomly divided into four groups (n = 6): three HFOV groups (3, 6, and 9 Hz) and one conventional mechanical ventilation (CMV) group. Standard lung recruitments were performed in all groups until optimal alveolar recruitment was reached. After lung recruitment, the optimal mean airway pressure or positive end-expiratory pressure was determined with decremental pressure titration, 2 cm H2O every 10 min. Animals were ventilated for 4 h. RESULTS: After lung recruitment, sustained improvements in gas exchange and compliance were observed in all groups. Compared with the HFOV-3 Hz and CMV groups, the transpulmonary pressure and tidal volumes were statistically significantly lower in the HFOV-9 Hz group. The lung injury scores and wet/dry weight ratios were significantly reduced in the HFOV-9 Hz group compared with the HFOV-3 Hz and CMV groups. Expression of interleukin-1ß and interleukin-6 in the lung tissue, decreased significantly in the HFOV-9 Hz group compared with the HFOV-3 Hz and CMV groups. Malondialdehyde expression and myeloperoxidase activity in lung tissues in the HFOV-9 Hz group decreased significantly, compared with the HFOV-3 Hz and CMV groups. CONCLUSION: The use of HFOV at 9 Hz minimizes lung stress and tidal volumes, resulting in less lung injury and reduced levels of inflammatory mediators compared with the HFOV-3 Hz and CMV conditions.

[Assessment of central venous-to-arterial CO(2) difference during early goal-directed therapy in patients with septic shock].

OBJECTIVE: To detect the changes of central venous-to-arterial carbon dioxide difference (P(cv-a)CO(2)) during early goal-directed therapy (EGDT) in patients with septic shock and evaluate its' value in predicting adequate resuscitation and prognosis. METHODS: From April 2009 to October 2010, 26 septic shock patients were enrolled in the study. EGDT was performed in all the patients immediately after enrollment. According to the whether they achieved early goal with in the 6 hour or not, patients were separated to EGDT achievement and un-achievement groups. At the onset and after the 6 hours EGDT, mean arterial pressure (MAP), cardiac index (CI), central venous oxygen saturation (ScvO(2)), oxygen delivery (DO(2)), oxygen consumption (VO(2)), oxygen extraction ratio (O(2) ext), lactate, P(cv-a)CO(2) were recorded. The Acute Physiology and Chronic Health Evaluation II (APACHE II) score and 28 day mortality were compared between 2 groups. RESULTS: There were no significant difference of age and sex between the 15 patients who achieved early goals and 11 patients who did not. EGDT un-achievement patients had higher APACHE II score (21 ± 5) and 28 day mortality (9/11) when compared with EGDT achievement patients (t = 2.985, χ(2) = 4.547, P < 0.05). In EGDT un-achievement group, MAP, CI, DO(2), VO(2), O(2)ext, ScvO(2), Lac, P(cv-a)CO(2) were comparable between the onset and 6 hours after EGDT. However, in EGDT achievement group, MAP ((90 ± 9) mmHg (1 mmHg = 0.133 kPa)), CI ((4.0 ± 1.8) L×min(-1)×m(-2)), DO(2) ((596 ± 274) ml×min(-1)×m(-2)), ScvO(2) (76.9% ± 4.1%) increased, and P(cv-a)CO(2) ((4.2 ± 2.7) mmHg) decreased significantly after 6 hours of EGDT (t values were -3.393, -2.985, -2.103 and -3.195 respectively, all P < 0.05). The changes of P(cv-a)CO(2) between the onset and 6 hours after EGDT, demonstrated high value for predictability of outcome, according to the area under the ROC curve (AUC) was 0.839 (P = 0.004). As a predictor for death, increasing of P(cv-a)CO(2) after 6 hours of EGDT has a sensibility of 100% and specificity of 60%. CONCLUSIONS: Increasing of P(cv-a)CO(2) after EGDT purports inadequate tissue perfusion in patients with septic shock. Changes of P(cv-a)CO(2) during EGDT demonstrated a useful tool to evaluate adequate resuscitation and prognosis.

[Effects of different reference point on intra-abdominal pressure measurement in critically ill patients: a clinical trial].

OBJECTIVE: To investigate the effects of different reference point on intra-abdominal pressure (IAP) measurement. METHODS: Nine critically ill patients with risk of intra-abdominal hypertension (IAH) were studied from July 2008 to June 2010, all of the patients were equipped with abdominal cavity drain and urinary drainage tube. By which IAP was measured using direct and indirect methods respectively. The symphysis pubis, phlebostatic axis and the midaxillary line at the level of the iliac crest were defined as reference points. According to the different reference point, three sets of IAP measurements were obtained in the supine position with each method and kept as IAP(S), IAP(P), IAP(I). Bland-Altman method analysis and Pearson's correlation were performed to evaluate the relationships between results from different reference points with direct and indirect methods. Paired t-test was performed to evaluate the differences among different reference points. RESULTS: Sixty measurements of IAP(S), IAP(P) and IAP(I) were obtained. In direct measurement through abdominal cavity drain, IAP(I) (13.8 ± 3.9) mmHg (1 mmHg = 0.133 kPa) was significantly higher than IAP(P) (12.8 ± 3.6) mmHg and IAP(S) (9.1 ± 3.6) mmHg, P < 0.05; while in indirect measurement through urinary drainage tube, IAP(I) (12.7 ± 3.2) mmHg was significantly higher than IAP(P) (11.7 ± 2.9) mmHg and IAP(S) (7.9 ± 3.0) mmHg too, P < 0.05. In either direct or indirect method, IAP(P) was higher than IAP(S), P < 0.05. And good correlations were found among IAP(S), IAP(P) and IAP(I). CONCLUSIONS: In the supine position, pressure obtained via the bladder could reflect authentic IAP. But selection of reference point has great impact on IAP measurement.

[The effects of positive end-expiratory pressure targeting optimal oxygenation on local gas distribution and inflammation in dogs with acute respiratory distress syndrome].

OBJECTIVE: To evaluate the effects of positive end-expiratory pressure (PEEP) targeting optimal oxygenation on local gas distribution and inflammation in dogs with acute respiratory distress syndrome (ARDS). METHODS: ARDS was induced by saline alveoli-lavage and oleic acid intravenous. The animals were mechanical ventilated 4 h at optimal PEEP titrated by oxygenation. Computed tomography (CT) scans were performed before and after induction of ARDS and at the end the study. NF-κB was measured by electrophoretic mobility shift assay (EMSA), IL-6 and IL-10 were assessed by ELISA. Myeloperoxidase (MPO) and malondialdehyde (MDA) were measured. Pathological changes were examined under optical microscope. RESULTS: (1) Compared to baseline, total lung volumes decreased and nonaerated areas increased significantly after the induction of ARDS in both groups (P < 0.05). Compared with ARDS models, PEEP titrated to achieve optimal oxygenation resulted in greater lung recruitment but was accompanied with hyperinflation, hyperinflation occurred in non-dependent lung. Compared with oleic acid-injured ARDS, the changing of hyperinflated lung areas was increased markedly in saline lavage-injured ARDS (P < 0.05). (2) Compared with right lung ventral lower lobe, lung injury score was lower in right lung upper lobe. Histological injury in right lung dorsal lower lobe was severer than that in right lung upper lobe and right lung ventral lower lobe. NF-κB activation of right lung dorsal lower lobe was markedly higher than right lung upper lobe (P < 0.05). MPO and MDA were much higher with right lung dorsal lower lobe than right lung upper lobe and right lung ventral lower lobe (P < 0.05). Compared with right lung upper lobe and right lung ventral lower lobe, IL-6 and IL-10 increased markedly in right lung dorsal lower lobe (P < 0.05). CONCLUSIONS: Alveolar hyperinflation and aggravated lung injury in non-dependent region were occurred at PEEP targeting optimal oxygenation. Hyperinflation was more common in saline lavage-injured ARDS.

[Prospective research on the prognosis of septic shock based on the change of lactate concentration in arterial blood].

OBJECTIVE: To evaluate the correlation between the lactate in artery blood and lactate clearance rate and prognosis in patients with septic shock in intensive care unit (ICU). METHODS: Prospectively studied 221 consecutive patients with septic shock from December 2005 to December 2007, the diagnosis of septic shock was made based on the criteria of 2001 ACCP/SCCM. For inclusion in the study, we required admission of the patients within 24 h of septic shock diagnosed. The criteria for exclusion from the study were an age of less than 18 years, pregnancy, serious inadequacy of liver and renal, needing blood purification, or acidosis result of biguanides drugs, or do-not-resuscitate. The eligible patients assigned to early goal-directed therapy. The 6-, 24- and 72-hour lactate clearance rate were calculated, the relationship between the level of lactate, lactate clearance rate, the APACHE II score, the number of failed organ and the 28-day mortality were evaluated. RESULTS: One hundred and five patients with septic shock were admitted, 74 male and 31 female, the mean age was 70 +/- 12 years. The 28-day mortality was 54.3%. The average APACHE II score at baseline was 20 +/- 8, the number of failed organs was 3.0 +/- 1.1 and the average concentration of lactate in artery blood at baseline was (3.8 +/- 3.6) mmol/L. Significant differences of the lactate at 0-, 6-, 24- and 72-hour were found between death group and survival group. There were 69 patients whose lactate in artery blood at baseline was > 2 mmol/L, 24 survived. The lactate clearance rate of 6- and 24-hour in survival group were significantly higher than death group (P < 0.01, P < 0.05, respectively), but the lactate clearance rate of 72-hour was not (P > 0.05). By using a multivariate logistic regression analysis, it showed that the lactate clearance rate of 6-hour was the independent predictive factor of survival. The area under the receiver operating characteristic curve (ROC) was 0.564, 0.649, 0.754, 0.784, respectively according to the level of the lactate at 0-, 6-, 24-hour and the 6-hour lactate clearance rate. The cutoff of 6-hour lactate clearance rate was >or= 30.0%, resulting in a sensitivity of 60.0% and a specificity of 77.3%. CONCLUSIONS: Dynamic observation of lactate level is very important for the survival in the patients with septic shock. Patients with elevated lactate and not decreased rapidly have a worse outcome. The 6-hour lactate clearance rate might be the indicator for predicting the prognosis of patients with septic shock.

[Assessment of stroke volume variation and intrathoracic blood volume index on the responsiveness to volume loading in mechanically ventilated canine with hemorrhagic shock].

OBJECTIVE: To assess the significance of stroke volume variation (SVV) and intrathoracic blood volume index (ITBI) on the responsiveness to volume loading in mechanically ventilated canine with hemorrhagic shock. METHODS: Hemorrhagic shock canine model was established with the modified Wiggers' method. The heart rate (HR), mean artery pressure (MAP), central venous pressure (CVP), pulmonary artery wedge pressure (PAWP), intrathoracic blood volume index (ITBI) and stroke volume variation (SVV) were investigated by Swan-Ganz catheter or PiCCO monitor. Graded volume loading (VL) was performed. Successive responsive VLs were performed (increase in SV > 5% after VL) until continuous change in SV < 5% (unresponsive) was reached. RESULTS: Fourteen canines were studied and a total of 134 VLs were performed. In 94 VLs, an increase in SV of more than 5% was reached. In the other 40 VLs, increase in SV was less than 5%. The change of HR, MAP, ITBI, SVV in responsive were more than those of unresponsive after VL. The change of CVP, PAWP in responsive were less than those of unresponsive. Significant correlation was found between DeltaSV after VL and the baseline values of ITBI, SVV. No correlation was found between DeltaSV and HR, MAP, CVP, PAWP. Significant correlations were also found between DeltaSV and DeltaCVP, DeltaPAWP, DeltaITBI, DeltaSVV after fluid loading. No correlation was found between DeltaSV and DeltaHR, DeltaMAP. By using receiver operating characteristic analysis, the area under the curve were 0.872 for SVV and 0.689 for ITBI, more than those of HR, MAP, CVP, PAWP statistically. As SVV value of 9.5% or more will predict an increase in the SV of at least 5% in response to a VL with a sensitivity of 92.6% and a specificity of 82.5%. CONCLUSIONS: SVV and ITBI were more useful indicators than CVP and PAWP on the assessment of responsiveness to volume loading. SVV as a functional preload parameter and for on-line monitoring may help to improve the hemodynamic management.