Quantitative evaluation of myocardial layer-specific strain using two-dimensional speckle tracking echocardiography in septic patients.

BACKGROUND: Although global longitudinal strain (GLS) is proven to be reduced and associated with adverse outcomes in septic patients, it has not been elucidated whether or not layer-specific strains are reduced. We aimed to explore the layer-specific strains of left ventricular (LV) for assessing myocardial dysfunction in septic patients. METHODS: A prospective observational study of patients with sepsis was conducted in a tertiary hospital in China. Routine two-dimensional speckle tracking echocardiography was performed within 24 h of enrollment. Demographic data, laboratory values, and clinical outcomes were collected. RESULTS: We recruited 79 septic patients finally. The mean age of septic patients was 59.4 years old and 45 (57.0%) were male. The median Acute Physiology Age and Chronic Health Evaluation (APACHE II) score, and mean sequential organ failure assessment (SOFA) score of all patients were 19.0 and 7.7, respectively. According to the left ventricular ejection fraction (LVEF) value of 50%, the patients were categorized into two groups: SICM (sepsis-induced cardiomyopathy, LVEF < 50%, n = 22) and non-SICM group ( LVEF ≥ 50%, n = 57). The median LVEF of SICM and non-SICM patients were 41.9% and 58.7%, and SICM patients had less negative layer-specific strain and global strain than that of non-SICM patients. The echocardiographic comparison of non-SICM and healthy controls was conducted to explore the myocardial injuries of non-SICM patients and the non-SICM had worse LS-epi than that of controls (-18.5% vs. -21.4%, p = 0.024). CONCLUSION: There were 72.2% (57) septic patients presented with non-SICM (LVEF ≥ 50%), and the strain value of epicardium of them was less negative than healthy controls.

mTOR/STAT-3 pathway mediates mesenchymal stem cell-secreted hepatocyte growth factor protective effects against lipopolysaccharide-induced vascular endothelial barrier dysfunction and apoptosis.

Mesenchymal stem cells (MSCs) protect the endothelial barrier complex and survival, implicated in the pathogenesis of acute lung injury (ALI) via paracrine hepatocyte growth factor (HGF). However, the mechanism of HGF in endothelial regulation remains unclear. Here, we introduced a coculture protocol of pulmonary microvascular endothelial cells (PMVECs) and overexpression of the HGF gene of MSCs (MSC-HGF). Immunofluorescence and endothelial permeability analysis revealed that MSC-HGF protected endothelial tight junction protein occludin expression and attenuated cellular permeability as well as endothelial apoptosis. To investigate the novel mechanism mammalian TOR (mTOR)/ signal transducer and activator of transcription 3 (STAT-3) signaling in HGF protective effects against endothelial barrier and apoptosis, we used recombinant mouse HGF in endothelial cells. In addition, we used mTOR inhibitor rapamycin to inhibit the mTOR pathway. Our study demonstrated that rapamycin decreased the protective effects of HGF on the endothelium by decreasing tight junction protein occludin expression and cell proliferation, and raising lipopolysaccharide (LPS)-induced endothelial permeability, endothelial cell injury factors ET-1 and vWF. Similarly, the protective effects of HGF on reducing endothelial barrier and apoptosis were weakened when PMVECs were treated with the STAT-3 inhibitor S3I-201. Moreover, mTOR/STAT-3 were activated by HGF demonstrated as raising mTOR (Ser2448) and STAT3 (Ser727) phosphorylation proteins, leading to endothelial barrier improvement and survival. Reversely, rapamycin or S3I-201 inhibited mTOR/STAT-3 activation. Taken together, our findings highlight that the activation of the mTOR/STAT-3 pathway provides novel mechanistic insights into MSC-secreted HGF protection against LPS-induced vascular endothelial permeability dysfunction and apoptosis, which contributes to decreasing microvascular loss and lung injury.

Effect of surfactant administration on outcomes of adult patients in acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Surfactant is usually deficiency in adult acute respiratory distress syndrome(ARDS) patients and surfactant administration may be a useful therapy. The aim of this study was to perform a meta-analysis of the effect of surfactant administration on outcomes of adult patients with acute respiratory distress syndrome. METHODS: PubMed, EMBASE, Medline, Cochrane database, Elsevier, Web of Science and http://clinicaltrials.gov were searched and investigated until December 2017. Randomized controlled trials(RCTs) comparing surfactant administration with general therapy in adult patients with ARDS were enrolled. The primary outcome was mortality (7-10-day, 28-30-day and 90-180-day). Secondary outcome included oxygenation (PaO2/FiO2 ratio). Demographic variables, surfactant administration, and outcomes were retrieved. Sensitivity analyses were used to evaluate the impact of study quality issues on the overall effect. Funnel plot inspection, Egger's and Begger's test were applied to investigate the publication bias. Internal validity was assessed with the risk of bias tool. Random errors were evaluated with trial sequential analysis(TSA). Quality levels were assessed by Grading of Recommendations Assessment, Development, and Evaluation methodology(GRADE). RESULTS: Eleven RCTs with 3038 patients were identified. Surfactant administration could not improve mortality of adult patients [Risk ratio (RR) (95%CI)) = 1.02(0.93-1.12), p = 0.65]. Subgroup analysis revealed no difference of 7-10-day mortality [RR(95%CI)) = 0.89(0.54-1.49), p = 0.66], 28-30-day mortality[RR(95%CI) = 1.00(0.89-1.12), p = 0.98] and 90-180-day mortality [RR(95%CI) = 1.11(0.94-1.32), p = 0.22] between surfactant group and control group. The change of the PaO2/FiO2 ratio in adult ARDS patients had no difference [MD(95%CI) = 0.06(- 0.12-0.24), p = 0.5] after surfactant administration. Finally, TSA and GRADE indicated lack of firm evidence for a beneficial effect. CONCLUSIONS: Surfactant administration has not been shown to improve mortality and improve oxygenation for adult ARDS patients. Large rigorous randomized trials are needed to explore the effect of surfactant to adult ARDS patients.

Noninvasive Ventilation in Acute Hypoxemic Nonhypercapnic Respiratory Failure: A Systematic Review and Meta-Analysis.

OBJECTIVE: To evaluate the effectiveness of noninvasive ventilation in patients with acute hypoxemic nonhypercapnic respiratory failure unrelated to exacerbation of chronic obstructive pulmonary disease and cardiogenic pulmonary edema. DATA SOURCES: PubMed, EMBASE, Cochrane library, Web of Science, and bibliographies of articles were retrieved inception until June 2016. STUDY SELECTION: Randomized controlled trials comparing application of noninvasive ventilation with standard oxygen therapy in adults with acute hypoxemic nonhypercapnic respiratory failure were included. Chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients were excluded. The primary outcome was intubation rate; ICU mortality and hospital mortality were secondary outcomes. DATA EXTRACTION: Demographic variables, noninvasive ventilation application, and outcomes were retrieved. Internal validity was assessed using the risk of bias tool. The strength of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation methodology. DATA SYNTHESIS: Eleven studies (1,480 patients) met the inclusion criteria and were analyzed by using a random effects model. Compared with standard oxygen therapy, the pooled effect showed that noninvasive ventilation significantly reduced intubation rate with a summary risk ratio of 0.59 (95% CI, 0.44-0.79; p = 0.0004). Furthermore, hospital mortality was also significantly reduced (risk ratio, 0.46; 95% CI, 0.24-0.87; p = 0.02). Subgroup meta-analysis showed that the application of bilevel positive support ventilation (bilevel positive airway pressure) was associated with a reduction in ICU mortality (p = 0.007). Helmet noninvasive ventilation could reduce hospital mortality (p = 0.0004), whereas face/nasal mask noninvasive ventilation could not. CONCLUSIONS: Noninvasive ventilation decreased endotracheal intubation rates and hospital mortality in acute hypoxemia nonhypercapnic respiratory failure excluding chronic obstructive pulmonary disease exacerbation and cardiogenic pulmonary edema patients. There is no sufficient scientific evidence to recommend bilevel positive airway pressure or helmet due to the limited number of trials available. Large rigorous randomized trials are needed to answer these questions definitely.

The Effect of Early Goal-Directed Therapy on Outcome in Adult Severe Sepsis and Septic Shock Patients: A Meta-Analysis of Randomized Clinical Trials.

BACKGROUND: Whether early goal-directed therapy (EGDT) improves outcome in severe sepsis and septic shock remains unclear. We performed a meta-analysis of existing clinical trials to examine whether EGDT improved outcome in the resuscitation of adult sepsis patients compared with control care. METHODS: We searched for eligible studies using MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials, and Web of Science databases. Studies were eligible if they compared the effects of EGDT versus control care on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Data including mortality, sample size of the patients with severe sepsis and septic shock, and resuscitation end points were extracted. Data were analyzed using methods recommended by the Cochrane Collaboration Review Manager 4.2 software. Random errors were evaluated by trial sequential analysis (TSA). RESULTS: Nine studies compared EGDT with control care, and 5202 severe sepsis and septic shock patients were included. A nonsignificant trend toward reduction in the longest all-cause mortality was observed in the EGDT group compared with control care (relative risk, 0.89; 99% confidence interval, 0.74-1.07; P = 0.10). However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients (relative risk, 0.72; 99% confidence interval, 0.57-0.90; P = 0.0002). TSA indicated lack of firm evidence for a beneficial effect. CONCLUSIONS: In this meta-analysis, a nonsignificant trend toward reduction in the longest all-cause mortality in patients resuscitated with EGDT was noted. However, EGDT significantly reduced intensive care unit mortality in severe sepsis and septic shock patients. TSA indicated a lack of firm evidence for the results. More powered, randomized controlled trials are needed to determine the effects.

MSCs modified with ACE2 restore endothelial function following LPS challenge by inhibiting the activation of RAS.

Angiotensin (Ang) II plays an important role in the process of endothelial dysfunction in acute lung injury (ALI) and is degraded by angiotensin-converting enzyme2 (ACE2). However, treatments that target ACE2 to injured endothelium and promote endothelial repair of ALI are lacking. Mesenchymal stem cells (MSCs) are capable of homing to the injured site and delivering a protective gene. Our study aimed to evaluate the effects of genetically modified MSCs, which overexpress the ACE2 protein in a sustained manner via a lentiviral vector, on Ang II production in endothelium and in vitro repair of lipopolysaccharide (LPS)-induced endothelial injury. We found that the efficiency of lentiviral vector transduction of MSCs was as high as 97.8% and was well maintained over 30 passages. MSCs modified with ACE2 showed a sustained high expression of ACE2 mRNA and protein. The modified MSCs secreted soluble ACE2 protein into the culture medium, which reduced the concentration of Ang II and increased the production of Ang 1-7. MSCs modified with ACE2 were more effective at restoring endothelial function than were unmodified MSCs, as shown by the enhanced survival of endothelial cells; the downregulated production of inflammatory mediators, including ICAM-1, VCAM-1, TNF-α, and IL-6; reduced paracellular permeability; and increased expression of VE-cadherin. These data demonstrate that MSCs modified to overexpress the ACE2 gene can produce biologically active ACE2 protein over a sustained period of time and have an enhanced ability to promote endothelial repair after LPS challenge. These results encourage further testing of the beneficial effects of ACE2-modified MSCs in an ALI animal model.

The effect of mild induced hypothermia on outcomes of patients after cardiac arrest: a systematic review and meta-analysis of randomised controlled trials.

INTRODUCTION: Mild induced hypothermia (MIH) is believed to reduce mortality and neurological impairment after out-of-hospital cardiac arrest. However, a recently published trial demonstrated that hypothermia at 33 °C did not confer a benefit compared with that of 36 °C. Thus, a systematic review and meta-analysis of randomised controlled trials (RCTs) was made to investigate the impact of MIH compared to controls on the outcomes of adult patients after cardiac arrest. METHODS: We searched the following electronic databases: PubMed/MEDLINE, the Cochrane Library, Embase, the Web of Science, and Elsevier Science (inception to December 2014). RCTs that compared MIH with controls with temperature >34 °C in adult patients after cardiac arrest were retrieved. Two investigators independently selected RCTs and completed an assessment of the quality of the studies. Data were analysed by the methods recommended by the Cochrane Collaboration. Random errors were evaluated with trial sequential analysis. RESULTS: Six RCTs, including one abstract, were included. The meta-analysis of included trials revealed that MIH did not significantly decrease the mortality at hospital discharge (risk ratio (RR) = 0.92; 95 % confidence interval (CI), 0.82-1.04; p = 0.17) or at 6 months or 180 days (RR = 0.94; 95 % CI, 0.73-1.21; p = 0.64), but it did reduce the mortality of patients with shockable rhythms at hospital discharge (RR = 0.74; 95 % CI, 0.59-0.92; p = 0.008) and at 6 months or 180 days. However, MIH can improve the outcome of neurological function at hospital discharge (RR = 0.80; 95 % CI, 0.64-0.98; p = 0.04) especially in those patients with shockable rhythm but not at 6 months or 180 days. Moreover, the incidence of complications in the MIH group was significantly higher than that in the control group. Finally, trial sequential analysis indicated lack of firm evidence for a beneficial effect. CONCLUSION: The available RCTs suggest that MIH does not appear to improve the mortality of patients with cardiac arrest while it may have a beneficial effect for patients with shockable rhythms. Although MIH may result in some adverse events, it helped lead to better outcomes regarding neurological function at hospital discharge. Large-scale ongoing trials may provide data better applicable to clinical practice.

A high mean arterial pressure target is associated with improved microcirculation in septic shock patients with previous hypertension: a prospective open label study.

INTRODUCTION: The effect of mean arterial pressure titration to a higher level on microcirculation in septic shock patients with previous hypertension remains unknown. Our goal is to assess the effect of mean arterial pressure titration to a higher level on microcirculation in hypertensive septic shock patients. METHODS: This is a single-center, open-label study. Hypertensive patients with septic shock for less than 24 hours after adequate fluid resuscitation and requiring norepinephrine to maintain a mean arterial pressure of 65 mmHg were enrolled. Mean arterial pressure was then titrated by norepinephrine from 65 mmHg to the normal level of the patient. In addition to hemodynamic variables, sublingual microcirculation was evaluated by sidestream dark field imaging. RESULTS: Nineteen patients were enrolled in the study. Increasing mean arterial pressure from 65 mmHg to normal levels was associated with increased central venous pressure (from 11 ± 4 to 13 ± 4 mmHg, P = 0.002), cardiac output (from 5.4 ± 1.4 to 6.4 ± 2.1 l/minute, P = 0.001), and central venous oxygen saturation (from 81 ± 7 to 83 ± 7%, P = 0.001). There were significant increases in small perfused vessel density (from 10.96 ± 2.98 to 11.99 ± 2.55 vessels/mm(2), P = 0.009), proportion of small perfused vessels (from 85 ± 18 to 92 ± 14%, P = 0.002), and small microvascular flow index (from 2.45 ± 0.61 to 2.80 ± 0.68, P = 0.009) when compared with a mean arterial pressure of 65 mmHg. CONCLUSIONS: Increasing mean arterial pressure from 65 mmHg to normal levels is associated with improved microcirculation in hypertensive septic shock patients. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01443494; registered 28 September 2011.

Stable genetic alterations of ß-catenin and ROR2 regulate the Wnt pathway, affect the fate of MSCs.

The Wnt pathways have been shown to be critical for the fate of mesenchymal stem cells (MSCs) in vitro, but their roles in MSCs in vivo remain poorly characterized due to the lack of stable alterations in their signaling. In the present study, we constructed long-term and stable mMSCs lines with activated and inactivated ß-catenin (the key molecule of the canonical Wnt signaling pathway) or ROR2 (the key molecule of the noncanonical Wnt5a/ROR2 signaling pathway) modifications with lentiviral vectors. We found that the transduction efficiencies mediated by the lentiviral vectors were 92.61-97.04% and were maintained over 20 passages of mMSCs. Transfection by lentiviral vectors not only regulated the mRNA and protein expression of ß-catenin or ROR2 but also regulated nuclear ß-catenin accumulation or the Wnt5a/JNK and Wnt5a/PKC pathways belonging to the canonical Wnt and noncanonical Wnt5a/ROR2 pathways, respectively. ß-Catenin or ROR2 gene overexpression promoted mMSC proliferation, migration and differentiation into osteoblasts, while inhibiting the adipogenic differentiation of mMSCs. In contrast, inactivation of the ß-catenin or ROR2 genes resulted in the opposite effects. Therefore, these results confirm that lentiviral vector transduction can facilitate sustained and efficient gene modification of the Wnt pathway in mMSCs. This study provides a method to investigate the effects of the Wnt pathway on the fate of mMSCs in vivo and for the further improvement of MSC-based therapies.

The effect of prone positioning on mortality in patients with acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

INTRODUCTION: Prone positioning (PP) has been reported to improve the survival of patients with severe acute respiratory distress syndrome (ARDS). However, it is uncertain whether the beneficial effects of PP are associated with positive end-expiratory pressure (PEEP) levels and long durations of PP. In this meta-analysis, we aimed to evaluate whether the effects of PP on mortality could be affected by PEEP level and PP duration and to identify which patients might benefit the most from PP. METHODS: Publications describing randomized controlled trials (RCTs) in which investigators have compared prone and supine ventilation were retrieved by searching the following electronic databases: PubMed/MEDLINE, the Cochrane Library, the Web of Science and Elsevier Science (inception to May 2013). Two investigators independently selected RCTs and assessed their quality. The data extracted from the RCTs were combined in a cumulative meta-analysis and analyzed using methods recommended by the Cochrane Collaboration. RESULTS: A total of nine RCTs with an aggregate of 2,242 patients were included. All of the studies received scores of up to three points using the methods recommended by Jadad et al. One trial did not conceal allocation. This meta-analysis revealed that, compared with supine positioning, PP decreased the 28- to 30-day mortality of ARDS patients with a ratio of partial pressure of arterial oxygen/fraction of inspired oxygen ≤ 100 mmHg (n = 508, risk ratio (RR) = 0.71, 95 confidence interval (CI) = 0.57 to 0.89; P = 0.003). PP was shown to reduce both 60-day mortality (n = 518, RR = 0.82, 95% CI = 0.68 to 0.99; P = 0.04) and 90-day mortality (n = 516, RR = 0.57, 95% CI = 0.43 to 0.75; P < 0.0001) in ARDS patients ventilated with PEEP ≥ 10 cmH2O. Moreover, PP reduced 28- to 30-day mortality when the PP duration was >12 h/day (n = 1,067, RR = 0.73, 95% CI = 0.54 to 0.99; P = 0.04). CONCLUSIONS: PP reduced mortality among patients with severe ARDS and patients receiving relatively high PEEP levels. Moreover, long-term PP improved the survival of ARDS patients.

Comparison of the effects of albumin and crystalloid on mortality in adult patients with severe sepsis and septic shock: a meta-analysis of randomized clinical trials.

INTRODUCTION: The aim of this study was to examine whether albumin reduced mortality when employed for the resuscitation of adult patients with severe sepsis and septic shock compared with crystalloid by meta-analysis. METHODS: We searched for and gathered data from MEDLINE, Elsevier, Cochrane Central Register of Controlled Trials and Web of Science databases. Studies were eligible if they compared the effects of albumin versus crystalloid therapy on mortality in adult patients with severe sepsis and septic shock. Two reviewers extracted data independently. Disagreements were resolved by discussion with other two reviewers until a consensus was achieved. Data including mortality, sample size of the patients with severe sepsis, sample size of the patients with septic shock and resuscitation endpoints were extracted. Data were analyzed by the methods recommended by the Cochrane Collaboration Review Manager 4.2 software. RESULTS: A total of 5,534 records were identified through the initial search. Five studies compared albumin with crystalloid. In total, 3,658 severe sepsis and 2,180 septic shock patients were included in the meta-analysis. The heterogeneity was determined to be non-significant (P = 0.86, I(2) = 0%). Compared with crystalloid, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin (odds ratio (OR) 0.88; 95% CI, 0.76 to 1.01; P = 0.08). However, the use of albumin for resuscitation significantly decreased 90-day mortality in septic shock patients (OR 0.81; 95% CI, 0.67 to 0.97; P = 0.03). Compared with saline, the use of albumin for resuscitation slightly improved outcome in severe sepsis patients (OR 0.81; 95% CI, 0.64 to 1.08; P = 0.09). CONCLUSIONS: In this meta-analysis, a trend toward reduced 90-day mortality was observed in severe sepsis patients resuscitated with albumin compared with crystalloid and saline. Moreover, the 90-day mortality of patients with septic shock decreased significantly.

Activation of canonical wnt pathway promotes differentiation of mouse bone marrow-derived MSCs into type II alveolar epithelial cells, confers resistance to oxidative stress, and promotes their migration to injured lung tissue in vitro.

The differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells in vivo and in vitro, is critical for reepithelization and recovery in acute lung injury (ALI), but the mechanisms responsible for differentiation are unclear. In the present study, we investigated the role of the canonical wnt pathway in the differentiation of mouse bone marrow-derived MSCs (mMSCs) into AT II cells. Using a modified co-culture system with murine lung epithelial-12 (MLE-12) cells and small airway growth media (SAGM) to efficiently drive mMSCs differentiation, we found that GSK 3ß and ß-catenin in the canonical wnt pathway were up-regulated during differentiation. The levels of surfactant protein (SP) C, SPB, and SPD, the specific markers of AT II cells, correspondingly increased in mMSCs when Wnt3a or LiCl was added to the co-culture system to activate wnt/ß-catenin signaling. The expression of these factors was depressed to some extent by inhibiting the pathway with the addition of DKK 1. The differentiation rate of mMSCs also depends on their abilities to accumulate and survive in inflammatory tissue. Our results suggested that the activation of wnt/ß-catenin signaling promoted mMSCs migration towards ALI mouse-derived lung tissue in a Transwell assay, and ameliorated the cell death and the reduction of Bcl-2/Bax induced by H(2) O(2), which simultaneously caused reduced GSK 3ß and ß-catenin in mMSCs. These data supports a potential mechanism for the differentiation of mMSCs into AT II cells involving canonical wnt pathway activation, which may be significant to their application in ALI.

[The value of nitrogen washout/washin method in assessing alveolar recruitment volume in acute lung injury patients].

OBJECTIVE: To evaluate the precision and feasibility of nitrogen washout/washin method in assessing lung recruitment of acute lung injury (ALI) patients. METHODS: Fifteen ALI patients underwent mechanical ventilation were involved. Two positive end-expiratory pressure (PEEP) levels (high and low) were adjusted according to ARDSnet recommendations or measurement of transpulmonary pressure, each for 30 minutes. Tidal volume (Vt), plateau of airway pressure (Pplat), other respiratory mechanics, gas-exchange and hemodynamics were measured. End expiration lung volume (EELV) was measured at different PEEP levels through nitrogen washout/washin method, and formula (EELVhighPEEP-EELVlowPEEP)-VtlowPEEP/(PplatlowPEEP-PEEPlowPEEP)×(PEEPhigh-PEEPlow) was used as recruitment (Rec-N2). Alveolar recruitment was measured using pressure-volume (P-V) curves (Rec-mes). Correlation and consistency of Rec-N2 and Rec-mes were compared by correlation analysis and Bland-Altman technique. RESULTS: PEEP titrated by ARDSnet recommendations or transpulmonary pressure were (7 ± 2) cm H2O (1 cm H2O = 0.098 kPa) vs (14 ± 5) cm H2O (P = 0.008); and there were significant differences in peak pressure (23 ± 5) cm H2O vs (28 ± 6) cm H2O, plateau of airway pressure (17 ± 4)cm H2O vs (22 ± 6) cm H2O, esophageal pressure, transpulmonary pressure and other respiratory mechanics between the two PEEP levels (P < 0.05). The P-V curve technique gave Rec-mes a value of 100 (-25 ∼ 185)ml. The nitrogen washout/washin technique gave Rec-N2 a value of 180 (-19 ∼ 255) ml, which showed a good correlation with a bias of 46 (8 ∼ 80) ml (R(2) = 0.755, P < 0.0001). CONCLUSION: Nitrogen washout/washin technique can be used to determine lung recruitment volume of ALI patients.

[Effects of gastric versus small bowel feeding on hospital acquired pneumonia in critically ill patients: a meta-analysis].

OBJECTIVE: To explore whether or not small bowel feeding can reduce the incidence of hospital acquired pneumonia (HAP). METHODS: The databases of Pubmed, Embase and Web of Science were searched to identify the relevant randomized controlled trials (RCT) from January 1992 to September 2012. Meta analysis was performed to analyze the effects of gastric versus small bowel feeding on HAP. RESULTS: Ten RCTs including 830 patients were retrieved and 6 of which examined the effect of ventilator-associated pneumonia (VAP). In total, the incidence of HAP was 15% (62/407) in bowel feeding group versus 23% (97/423) in gastric feeding group. As compared with gastric feeding, small bowel feeding appeared to significantly reduce the incidence of HAP [RR 0.67, 95%CI(0.51-0.89), P = 0.005; I(2) = 0%)], but did not reduce the mortality [RR 1.08, 95%CI(0.84-1.40), P = 0.54; I(2) = 0%] and the duration of ICU stay [weighted mean difference in 0.04 days, 95%CI(-2.83-2.91), P = 0.98; I(2) = 96%]. Subgroup analysis indicated that small bowel nutrition reduced the incidence of VAP [RR 0.64, 95%CI(0.46-0.90), P = 0.01; I(2) = 9%)], but did not reduce the incidence HAP of non-VAP [RR 0.74, 95%CI(0.45-1.21), P = 0.23; I(2) = 0%)]. CONCLUSION: Compared with gastric feeding, small bowel feeding can reduce the incidence of HAP, especially VAP, but can not reduce the mortality.

[The evaluation value of severity and prognosis of septic shock patients based on the arterial-to-venous carbon dioxide difference].

OBJECTIVE: To assess the value of central venous-to-arterial carbon dioxide difference [P((cv-a))CO2] in evaluation of disease severity and prognosis in patients with septic shock. METHODS: There were 45 consecutive resuscitated septic shock patients from April 2009 to October 2010 included immediately after their admission into our ICU. The patients were divided into low P((cv-a))CO2 group and high P((cv-a))CO2 group according to a threshold of 6 mm Hg (1 mm Hg = 0.133 kPa). All patients were treated by early goal directed therapy (EGDT). The parameters of hemodynamics, lactate clearance rate, the Acute Physiology and Chronic Health Evaluation II (APACHE II) score, the sequential organ failure assessment (SOFA) score, 6 h rate of EGDT achievement, the ICU mortality and 28 days in-hospital mortality were recorded for all patients. RESULTS: There were 30 patients in the low P((cv-a))CO2 group, and 15 in the high P((cv-a))CO2 group. There were no significant differences between low P((cv-a))CO2 and high P((cv-a))CO2 patients in age, APACHE II score and SOFA score (all P > 0.05). Compared with the high P((cv-a))CO2 group, the low P((cv-a))CO2 group had higher cardiac index (CI) and 24 h CI, higher delivery O2 (DO2) and 24 h DO2, higher central venous oxygen saturation (ScvO2) [(74 ± 9)% vs (67 ± 8)%], lower lactate [(3.4 ± 2.1) mmol/L vs (5.7 ± 4.5) mmol/L] and higher ΔSOFA score [(0.7 ± 1.8) vs (-0.4 ± 1.1)], lower 24 h SOFA score [(7.8 ± 2.0) vs (9.8 ± 2.0)], higher 6 h rate of EGDT achievement (83.3% vs 53.3%) (P < 0.05), however, there were no differences in 28 days mortality and ICU mortality between the two groups (P > 0.05). CONCLUSION: P((cv-a))CO2 might be an indicator for predicting the severity of patients with septic shock and evaluating tissue perfusion.

[The effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome combined with critical illness-related corticosteroid insufficiency].

OBJECTIVE: To investigate the effect of stress dose glucocorticoid on patients with acute respiratory distress syndrome (ARDS) combined with critical illness-related corticosteroid insufficiency (CIRCI). METHODS: All early ARDS patients combined with CIRCI were screened by an adrenal corticotrophic hormone (ACTH) test and randomly divided into treatment group (hydrocortisone 100 mg intravenous, 3 times/day, consecutively for 7 days, n = 12) and control group (equivalent normal saline, n = 14). General clinical data, changes of arterial blood gas, hemodynamics and respiratory mechanics were observed and recorded at admission and at 7 days after treatment. Ventilator-free and shock-free days, ICU stay within 28 days after admission were recorded and 28-day mortality was used as judge prognosis index. RESULTS: CIRCI rate in 45 early ARDS patients was 57.8% (26 patients), and the shock rate was markedly higher in ARDS patients with CIRCI than patients without CIRCI (46.2% vs 5/19). There were no significant differences in baseline parameters, oxygenation and illness severity between the treatment and control groups, except for markedly lower lactic level in the treatment group [2.7(1.2, 3.9) mmol/L vs 4.6(2.5, 6.3) mmol/L, P < 0.05]. After 7 days of treatment, PaO2/FiO2 markedly increased, while heart rate obviously decreased in the both groups. Compared with the control group, survival time of patients was significantly longer and shock rate of the patients was markedly lower in treatment group within 28 days (5/12 vs 10/14, P < 0.05). The 28-day mortality, which were adjusted by baseline arterial lactic, was lower in the treatment group (2.6/12) than in the control group (5.8/14) while with no significant difference (P > 0.05). There was no significant difference in complication incidence between the two groups. CONCLUSION: Stress dose glucocorticoid could reduce shock incidence and prolong survival time, and has a tendency of lower 28-day mortality in early ARDS patients combined with CIRCI.

[Effect of Xuebijing injection treatment on acute respiratory distress syndrome: a multicenter prospective randomized control clinical trial].

OBJECTIVE: To assess the therapeutic effect of Xuebijing injection on adult patients with acute respiratory distress syndrome (ARDS). METHODS: A multicenter prospective randomized control study was conducted at 10 intensive care units in Jiangsu province. A total of 172 early ARDS patients were randomly divided into Xuebijing treatment and control groups. All patients received routine therapy of ARDS while additional Xuebijing injection 100 ml was administered in the treatment group intravenously for 7 days. Lung injury score, acute physiology and chronic health evaluation II (APACHE II) score, multiple organ dysfunction score (MODS) and PaO2/FiO2 of the patients was recorded before and after treatment. Mortality at 28 days and the duration of mechanical ventilation were compared between two groups. RESULTS: Ninety-one patients were assigned to receive Xuebijing injection and 81 patients as control; Mortality at Days 28 and 90, the duration of mechanical ventilation and ventilation free days showed no difference between two groups (P > 0.05). PaO2/FiO2 improved after randomization versus pre-treatment in all patients. There was no significant difference between two groups. Murray scores were not significantly different between two groups. In a subgroup analysis of patients with pulmonary infection, pulmonary contusion and extra-pulmonary cause, two groups had no difference in mortality at Day 28, mortality at Day 90, the duration of mechanical ventilation, ventilation free days and days of ICU stay (P > 0.05). CONCLUSION: The treatment of Xuebijing injection early in course of ARDS does not improve the mortality of ARDS patients. But it may improve lung function and oxygenation. Further studies are warranted.

[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.

[A meta-analysis of the effects of direct hemoperfusion with polymyxin B-immobilized fiber on prognosis in severe sepsis].

OBJECTIVE: To investigate the effects of direct hemoperfusion with polymixin B-immobilized fiber (DHP-PMX) in patients with sepsis. METHODS: We searched Pubmed, Embase, Web of Science databases and identified relevant randomized controlled trials (RCT) from January 1995 to May 2010. Meta-analysis of DHP-PMX on mortality and levels of endotoxin in patients with sepsis were conducted using the methods recommended by the Cochrane Collaboration. RESULTS: Eleven RCTs were included. Eight of them included the mortality of patients (sample size: 211 DHP-PMX and 178 conventional medical therapy). In total, the mortalities of patients with sepsis in DHP-PMX group and conventional group were 37.4% (79/211) and 68.5% (122/178) respectively. Compared with the conventional medical therapy, DHP-PMX appeared to significantly reduce mortality (OR = 0.24, 95%CI 0.16 - 0.38, P < 0.000 01). The results were similar when two RCTs enrolling patients with methicillin resistant staphylococcus aureus (MRSA) infections were excluded (OR = 0.27, 95%CI 0.17 - 0.45, P < 0.000 01). When the analysis was limited to the nine studies that reported 28- to 30-day mortality, results were unchanged (OR = 0.29, 95%CI 0.17 - 0.48, P < 0.000 01). Six RCTs had the available data of endotoxin. The level of endotoxin decreased 31 ng/L(95%CI 22.46 - 39.55) after DHP-PMX therapy, and the decreasing was statistically significant (P < 0.000 01), while the level of endotoxin in patients of conventional group did not change (P = 0.94). CONCLUSIONS: This study suggests a favorable effects of DHP-PMX on mortality and endotoxin decreasing in patients with sepsis. However, lack of enough cases and blinding need to be considered. Further investigation with large sample of high quality RCTs is needed.

[Dead space guided positive end-expiratory pressure in patients with acute respiratory distress syndrome].

OBJECTIVE: To evaluate the value of dead space fraction (V(D)/V(T)) guided positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome (ARDS). METHODS: Twenty-three intubated and mechanically ventilated patients with early ARDS were enrolled in the study. PEEP was titrated by lowest V(D)/V(T). Parameters of oxygenation and respiratory mechanics were observed. RESULTS: PEEP titrated by lowest V(D)/V(T) and highest static lung compliance (C(Lst)) (P > 0.05) respectively, were lower than PEEP titrated by optimal oxygenation (P < 0.05), but there was no significant difference between lowest V(D)/V(T) and highest C(Lst) method. The V(D)/V(T) that ventilated on PEEP titrated by the lowest V(D)/V(T) decreased than its basal level. There was no difference significantly between the V(D)/V(T) that ventilated on PEEP elected by the other two methods with basal level (P > 0.05). The the ratio of arterial PO2 to the inspired oxygen fraction (PaO2/FiO2) ratios improved significantly than the baseline values in three ventilation strategies, and that ventilated on PEEP targeting the lowest V(D)/V(T) was lower than PEEP targeting optimal oxygenation. The plateau airway pressure that ventilated on PEEP targeting optimal oxygenation was higher than the other two methods. The functional residual capacity (FRC) of patients ventilated by PEEP targeting optimal oxygenation was increased than the lowest V(D)/V(T) and maximum C(Lst). CONCLUSIONS: V(D)/V(T) could be one of the methods to titrate the optimal PEEP in patients with early ARDS. Optimal PEEP targeting the highest compliance in conjunction with the lowest dead space fraction indicated a maximum amount of effectively expanded alveoli.