Guohao Xie

Epidemiology of severe sepsis in critically ill surgical patients in ten university hospitals in China

Objectives:To determine the occurrence rate, outcomes, and the characteristics of severe sepsis in surgical intensive care units in multiple medical centers within China and to assess the cost and resource use of severe sepsis in China. Design and Setting:Prospective, observational study of surgical intensive care unit patients at ten university hospitals in six provinces in China. Patients:All adult admissions in studied intensive care units from December 1, 2004, to November 30, 2005. Interventions:None. Measurements and Main Results:The criteria of severe sepsis were based on the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference definition. Analysis of data from 3,665 intensive care unit admissions identified 318 (8.68%) cases of severe sepsis, 64.8% of which were men. The median age (interquartile range) of patients with severe sepsis was 64 (47–74) yrs. Microbes had been isolated from 228 (71.7%) patients, including 171 (53.8%) with Gram-negative bacteria and 146 (45.9%) with Gram-positive bacteria. A total of 90 (22.0%) patients had invasive fungal infection, 20 (6.3%) of which had fungemia. The abdomen was the most common site of infections (72.3%), followed by lung (52.8%). The overall hospital mortality of severe sepsis was 48.7%. Risk factors for hospital mortality included age, chronic comorbidity of malignant neoplasm, Gram-positive bacterial infection, invasive fungal infection, admission Acute Physiology Score, and admission Sequential Organ Failure Assessment score of respiratory dysfunction and cardiovascular dysfunction. The median Therapeutic Intervention Scoring System-28 score was 43 (38–49). The mean hospital cost was

Impact of invasive fungal infection on outcomes of severe sepsis: a multicenter matched cohort study in critically ill surgical patients

11,390 per patient and

Increased Genomic Copy Number of DEFA1/DEFA3 Is Associated with Susceptibility to Severe Sepsis in Chinese Han Population

502 per patient per day. Conclusions:Severe sepsis is a common, expensive, and frequently fatal syndrome in critically ill surgical patients in China. Other than the microbiological patterns, the incidence, mortality, and major characteristics of severe sepsis in Chinese surgical intensive care units are close to those documented in developed countries.

Effect of CYP3A4*1G on the fentanyl consumption for intravenous patient-controlled analgesia after total abdominal hysterectomy in Chinese Han population.

IntroductionFungal infection is increasingly common in critical illness with severe sepsis, but the influence of invasive fungal infection (IFI) on severe sepsis is not well understood. The aim of this study was to investigate the impact that IFI has on the outcomes of critically ill surgical patients with severe sepsis in China by means of matched cohort analysis; we also evaluated the epidemiologic characteristics of IFI in this population.MethodsRecords for all admissions to 10 university hospital surgical intensive care units (ICUs) from December 2004 to November 2005 were reviewed. Patients who met criteria for severe sepsis were included. IFI was identified using established criteria based on microbiologic or histological evidence. A matched cohort study was conducted to analyze the relationship between IFI and outcomes of severe sepsis.ResultsA total of 318 patients with severe sepsis were enrolled during the study period, of whom 90 (28.3%) were identified as having IFI. A total of 100 strains of fungi (58% Candida albicans) were isolated from these patients. Independent risk factors for IFI in patients with severe sepsis included mechanical ventilation (>3 days), Acute Physiology and Chronic Health Evaluation score, coexisting infection with both Gram-positive and Gram-negative bacteria, and urethral catheterization (>3 days). Compared with the control cohort, IFI was associated with increased hospital mortality (P < 0.001), high hospital costs (P = 0.038), and prolonged stay in the ICU (P < 0.001) and hospital (P = 0.020).ConclusionIFI is frequent in patients with severe sepsis in surgical ICUs and is associated with excess risk for hospital mortality, longer ICU and hospital stays, and greater consumption of medical resources.

Lack of association between TREM-1 gene polymorphisms and severe sepsis in a Chinese Han population

Background:Human neutrophil peptides 1–3 are endogenous cationic antimicrobial peptides implicated in host defense against microbes. The genes encoding human neutrophil peptides 1–3 (DEFA1/DEFA3) exhibit copy number variations. This study was designed to determine whether DEFA1/DEFA3 copy number variations conferred susceptibility to infection-induced complications such as severe sepsis. Methods:This case–control study was performed in 179 patients with severe sepsis and 233 healthy blood donors and was replicated in an independent cohort of 112 cases and 118 controls. Plasma levels of human neutrophil peptides 1–3, tumor necrosis factor-&agr;, interleukin-6, and interleukin-10 were detected. Results:The genotype of DEFA1/DEFA3 with more than eight copies was more frequent in patients with severe sepsis than in controls (55.9% vs. 31.3%; P = 1.13 × 10−6, odds ratio 2.77, 95% confidence interval 1.85–4.16). After adjustment for age and gender, logistic regression analysis confirmed the association of the genotype of more than eight copies with an increased risk of severe sepsis (P = 2.25 × 10−5, odds ratio 2.66, 95% confidence interval 1.69–4.19). This established association was replicated in a second age- and gender-matched case–control cohort (P = 0.02, odds ratio 1.90, 95% confidence interval 1.11–3.27). Furthermore, compared with those with fewer copies, the patients carrying more than eight copies of DEFA1/DEFA3 presented significantly lower plasma levels of human neutrophil peptides 1–3, tumor necrosis factor-&agr;, interleukin-6, and interleukin-10 (P = 0.039, 0.017, 0.030, and 0.029, respectively). Conclusions:DEFA1/DEFA3 is an important genetic component participating in host immune response to severe sepsis. A higher copy number of DEFA1/DEFA3 (>8 copies) is significantly associated with the risk of severe sepsis.

Dexmedetomidine vs propofol sedation reduces delirium in patients after cardiac surgery: A meta-analysis with trial sequential analysis of randomized controlled trials

What is known and Objective:  Clinical investigations into postoperative intravenous patient‐controlled analgesia (PCA) have indicated interindividual differences in fentanyl consumption. Cytochrome P450 3A4 (CYP3A4) is the main metabolism enzyme of fentanyl, and single nucleotide polymorphisms within the CYP3A4 gene may contribute to the variability of fentanyl analgesic efficacy. The aim of this study was to investigate whether the most common genetic variation in Chinese, CYP3A4*1G, has an impact on the fentanyl consumption for intravenous PCA in Chinese Han women undergone abdominal total hysterectomy.

Altered melatonin secretion and circadian gene expression with increased proinflammatory cytokine expression in early-stage sepsis patients.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a cell surface receptor expressed on neutrophils and monocytes. TREM-1 acts to amplify inflammation and serves as a critical mediator of inflammatory response in the context of sepsis. Blocking of TREM-1 can protect against sepsis in mice. To date, the predisposition of TREM-1 gene polymorphisms to sepsis has not been reported. This study was designed to investigate whether TREM-1 genomic variations were associated with the development of severe sepsis. Three common polymorphisms (rs7768162, rs9471535, and rs2234237) within the TREM-1 gene were detected in 175 patients with severe sepsis and in 139 healthy control subjects. Neither allelic frequencies nor genotype distributions of the assayed single nucleotide polymorphisms were found to be significantly different between patients and controls as well as between surviving and nonsurviving patients in different models of inheritance. The distributions of estimated haplotype patterns were also comparable between the defined groups. The present findings suggest that the three studied polymorphisms within the TREM-1 gene may not play a major role in the predisposition to severe sepsis in a Chinese Han cohort. Further replication studies with large sample size to achieve sufficient power (80%) to dismiss these polymorphisms as candidate markers for severe sepsis are warranted.

Sphingosine 1-phosphate Receptor 2 Signaling Suppresses Macrophage Phagocytosis and Impairs Host Defense against Sepsis.

Purpose: It is uncertain whether dexmedetomidine is better than propofol for sedation in postcardiac surgery patients. The purpose of this meta‐analysis was to compare the effects of dexmedetomidine and propofol sedation on outcomes in adult patients after cardiac surgery. Methods: Randomized controlled trials comparing outcomes in cardiac surgery patients sedated with dexmedetomidine or propofol were retrieved from PubMed, Embase, Web of Science, the Cochrane Library, and Clinicaltrials.Gov until May 23, 2016. Results: A total of 969 patients in 8 studies met the selection criteria. The results revealed that dexmedetomidine was associated with a lower risk of delirium (risk ratio, 0.40;95% confidence interval [CI], 0.24‐0.64; P = .0002), a shorter length of intubation (hours; mean difference, −0.95; 95% CI, −1.26 to −0.64; P < .00001), but a higher incidence of bradycardia (risk ratio 3.17; 95% CI, 1.41‐7.10; P = .005) as compared to propofol. There were no statistical differences in the incidence of hypotension or atrial fibrillation, or the length of intensive care unit stay between dexmedetomidine and propofol sedation regimens. Conclusions: Dexmedetomidine sedation could reduce postoperative delirium and was associated with shorter length of intubation, but might increase bradycardia in patients after cardiac surgery compared with propofol.

Dexmedetomidine Versus Propofol Sedation Improves Sublingual Microcirculation After Cardiac Surgery: A Randomized Controlled Trial.

Inflammatory and immune responses, as well as melatonin secretion, are affected by circadian regulation. Abnormal circadian rhythm of melatonin release has been reported to be associated with the later stages of sepsis; however, its role in the early stages of sepsis is unclear. We studied 11 septic and 11 non-septic patients in our intensive care unit (ICU). Peripheral blood was drawn at 4-h intervals on the first day, beginning at 2:00 p.m., over a total period of 24 h. Plasma levels of melatonin, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). Messenger RNA levels of circadian genes Cry-1 and Per-2 were analyzed using quantitative real-time PCR. Results show the circadian rhythm of melatonin secretion was altered in the early stages of sepsis. The melatonin secretion acrophase occurred earlier in septic patients at 6:00 p.m., compared with at 2:00 a.m. in non-septic ICU patients. Compared with the non-septic group, both Cry-1 and Per-2 expression were significantly decreased while TNF-α and IL-6 expression were significantly increased in septic patients [TNF-α, 64.1 (43.6-89.1) vs. 11.4 (10.4-12.5) ng/ml; IL-6, 41.2 (35.7-50.8) vs. 19.1 (16-136.7) ng/ml; median (range), both P=0.04]. The peak concentrations of TNF-α and IL-6 were shown to be in concordance with the rhythm of melatonin secretion. The circadian rhythm of melatonin secretion and circadian gene expression were altered in the early stages of sepsis, which likely led to the changes in pro-inflammatory cytokine release. These findings shed light on the potential link between circadian rhythm and the progression of early-stage sepsis.

Intensive insulin therapy for septic patients: a meta-analysis of randomized controlled trials.

Background:Sepsis is characterized by an inappropriate systemic inflammatory response and bacteremia that promote multiorgan failure and mortality. Sphingosine 1-phosphate receptor 2 (S1PR2) modulates endotoxin-induced inflammation in endothelium. However, as a highly expressed S1P receptor in macrophages, its role in regulating macrophage response to bacterial infection remains unclear. Methods:Cecal ligation and puncture or intratracheal instillation of Escherichia coli was induced in wild-type or S1pr2-deficient mice. The antibacterial ability of cell-specific S1PR2 was tested in bone marrow reconstitution mice or mice with macrophage-specific deletion. Signaling molecules responsible for S1PR2-mediated phagocytosis were also measured in the bone marrow–derived macrophages. In addition, S1PR2 expression levels and its correlation with severity of sepsis were determined in critically ill patients (n = 25). Results:Both genetic deletion and pharmaceutical inhibition of S1PR2 significantly limited bacterial burden, reduced lung damage, and improved survival (genetic deletion, 0% in S1pr2+/+ vs. 78.6% in S1pr2−/−, P < 0.001; pharmaceutical inhibition, 9.1% in vehicle vs. 22.2% in S1PR2 antagonist, P < 0.05). This protection was attributed to the enhanced phagocytic function of S1PR2-deficient macrophages (mean fluorescent intensity, 2035.2 ± 202.1 vs. 407.8 ± 71.6, P < 0.001). Absence of S1PR2 in macrophage inhibits RhoA-dependent cell contraction and promotes IQGAP1-Rac1-dependent lamellipodial protrusion, whose signaling pathways depend on extracellular stimulators. In septic patients, increased S1PR2 levels in peripheral blood mononuclear cells were positively correlated with the severity of sepsis (r = 0.845, P < 0.001). Conclusions:This study implies that S1PR2, as a critical receptor in macrophage, impairs phagocytosis and antimicrobial defense in the pathogenesis of sepsis. Interventions targeting S1PR2 signaling may serve as promising therapeutic approaches for sepsis.