Glucocorticoid receptor mRNA levels are selectively decreased in neutrophils of children with sepsis

Objective  Corticosteroids are used in sepsis treatment to benefit outcome. However, discussion remains on which patients will benefit from treatment. Inter-individual variations in cortisol sensitivity, mediated through the glucocorticoid receptor, might play a role in the observed differences. Our aim was to study changes in mRNA levels of three glucocorticoid receptor splice variants in neutrophils of children with sepsis. Patients and design  Twenty-three children admitted to the pediatric intensive care unit with sepsis or septic shock were included. Neutrophils were isolated at days 0, 3 and 7, and after recovery (>3 months). mRNA levels of the glucocorticoid receptor splice variants GR-α (determining most of the cortisol effect), GR-P (increasing GR-α effect) and GR-β (inhibitor of GR-α) were measured quantitatively. Main results  Neutrophils from sepsis patients showed decreased levels of glucocorticoid receptor mRNA of the GR-α and GR-P splice variants on day 0 compared to after recovery. GR-α and GR-P mRNA levels showed a gradual recovery on days 3 and 7 and normalized after recovery. GR-β mRNA levels did not change significantly during sepsis. GR expression was negatively correlated to interleukin-6 (a measure of disease severity, r = −0.60, P = 0.009). Conclusions  Children with sepsis or septic shock showed a transient depression of glucocorticoid receptor mRNA in their neutrophils. This feature may represent a tissue-specific adaptation during sepsis leading to increased cortisol resistance of neutrophils. Our study adds to understanding the mechanism of cortisol sensitivity in immune cells. Future treatment strategies, aiming at timing and tissue specific regulation of glucocorticoids, might benefit patients with sepsis or septic shock.     

Soluble triggering receptor expressed on myeloid cells 1 as an anti-inflammatory mediator in sepsis

Objective To define the significance of soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in the septic cascade by comparing its kinetics to those of other proinflammatory mediators and of interleukin (IL) 10. Design Prospective study in a tertiary unit. Patients Blood was sampled from 90 patients with septic syndrome due to ventilator-associated pneumonia for 7 days after the appearance of symptoms. Concentrations of tumor necrosis factor (TNF) α, IL-6, IL-8, IL-10, and sTREM-1 were determined by enzyme-linked immunosorbent assay. Results Serum levels of TNFα, IL-6, IL-10, and sTREM-1 were higher in nonsurvivors than in survivors; similar differences were not found for IL-8. Positive correlations were found between the ratios IL-10/TNFα and sTREM-1/TNFα, between IL-10/IL-6 and sTREM-1/IL-6, and between IL-10/IL-8 and sTREM-1/IL-8. Median values of IL-10/TNFα upon presentation of sepsis, severe sepsis, and septic shock were 3.21, 2.16, and 2.86, respectively (NS). Respective values for sTREM-1/TNFα were 21.28, 7.33, and 27.78 (p = 0.047 between sepsis and severe sepsis, p = 0.003 between severe sepsis and septic shock). Conclusions sTREM-1 follows the kinetics of IL-10 and should therefore be considered an anti-inflammatory mediator in sepsis. Decreased ratios of sTREM-1/TNFα might determine transition from sepsis to severe sepsis and from severe sepsis to septic shock. This article refers to the editorial .     

Usefulness of presepsin (sCD14 subtype) measurements as a new marker for the diagnosis and prediction of disease severity of sepsis in the Korean population

Purpose

Presepsin has recently emerged as a new useful sepsis marker, and our study is focused on the usefulness of presepsin as earlier detection and monitoring biomarker for sepsis comparing with other conventional biomarkers.

Materials and methods

We compared the mean values of presepsin, procalcitonin, interleukin 6, and high-sensitivity C-reactive protein levels between infection group and noninfection group of study subjects and assessed whether the values decreased during treatment. Furthemore, we evaluated the diagnostic accuracy of presepsin in sepsis and compared the mean level of presepsin to the Acute Physiology and Chronic Health Evaluation III score and mortality rate on the 30th day.

Results

Mean presepsin levels were significantly different between infection group and noninfection group (1403.47 pg/mL vs 239.00 pg/mL). During treatment, mean levels of presepsin decreased significantly, and in the receiver operating characteristic curve analysis, the area under curve value of presepsin was significantly higher than that of other biomarkers. The presepsin levels did not correlate significantly with Acute Physiology and Chronic Health Evaluation III scores and mortality rates on the 30th day.

Conclusions

Presepsin showed significantly higher values in infection group than in noninfection group. The diagnostic accuracy of presepsin was higher than other conventional biomarkers. For early diagnosis and treatment of bacterial sepsis, presepsin could be a more useful marker than the other markers.     

谷氨酰胺对脓毒症小鼠氧化应激损伤的保护作用研究

目的：探讨谷氨酰胺是否可以减轻脓毒症小鼠的氧化应激损伤,从而为临床应用提供实验依据。方法按随机数字表采取完全随机化方法将5周龄雄性昆明小鼠分为对照组、模型组、谷氨酰胺组3组,每组10只。模型组与谷氨酰胺组腹腔注射内毒素5 mL/kg制备脓毒症模型,对照组腹腔注射等量生理盐水。制模成功后,谷氨酰胺组即刻尾静脉注射丙氨酰谷氨酰胺注射液0.75 g/kg,模型组和对照组尾静脉注射等量无菌生理盐水。6 h后终止实验,眼眶取血后处死动物,取血清和肝、肾组织匀浆检测氧化应激指标超氧化物酶歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）、丙二醛（MDA）。结果与对照组比较,模型组血清、肝、肾组织SOD活性、GSH-Px明显降低,MDA含量明显升高。与模型组比较,谷氨酰胺组血清、肝、肾组织SOD活性、GSH-Px明显升高,MDA含量明显降低〔血清SOD（U/mL）：134.78±3.74比124.60±3.49,肝脏SOD （U/mg）：56.71±1.35比49.84±0.86,肾脏SOD（U/mg）：46.22±1.22比43.22±1.52;血清GSH-Px（U/mL）：325.15±21.86比267.04±13.5,肝脏 GSH-Px（U/mg）：91.35±1.59比83.40±1.33,肾脏 GSH-Px（U/mg）：136.08±0.58比132.97±0.74;血清MDA（μmol/L）：9.20±0.32比13.67±1.24,肝脏MDA（nmol/mg）：1.85±0.10比4.88±0.17,肾脏MDA（nmol/mg）：2.47±0.12比3.52±0.27,均P＜0.01〕。结论脓毒症造成氧化应激与氧化损伤,使用谷氨酰胺可以提高抗氧化酶GSH-Px、SOD水平,增强抗氧化能力,减少脂质代谢产物MDA含量,减少有毒代谢产物,从而起到减少氧化应激损伤的作用。     

Evolving concepts in sepsis definitions

Developing effective therapies for any disease process relies on the ability to clearly define the population of patients who will benefit from that intervention. Advances in our understanding of sepsis pathogenesis have made it clear that the global definition or concept of sepsis as a single, homogeneous disease process is inadequate. The idea that all patients who have severe sepsis will respond positively to any single therapeutic intervention is probably too simple, although some interventions may target more general pathways and be globally beneficial. For example, drotrecogin alfa (activated) was shown to be effective at reducing mortality in a clinical trial with a heterogeneous patient population,(28) although even here positive results were restricted to patients who had severe sepsis, highlighting the importance of being able to better characterize patients. Our approach to sepsis and its definition has evolved as we increasingly recognize the complex nature of the process and the importance of targeting treatments according to individual patients' characteristics. Clinical variables are too sensitive and nonspecific and improved biologic and biochemical tools need to be incorporated into current definitions to provide precise and accurate methods of diagnosis. Systems, such as PIRO, that can characterize patients according to their likely prognosis and response to a specific therapy need to be further developed so that treatments can be appropriately directed for individual patients.     

Thiamine deficiency in critically ill patients with sepsis

ObjectiveThe objective of the study was to determine the prevalence of absolute thiamine deficiency (TD) in critically ill patients with sepsis and to examine the association between thiamine levels and lactic acidosis.DesignThis was a prospective, observational study.SettingThe setting was an urban, tertiary care center with approximately 50 000 emergency department visits per year and intensive care units numbering approximately 50 total beds.PatientsThirty study patients admitted with clinical suspicion of infection and evidence of tissue hypoperfusion, as defined by a lactic acid level greater than 4 mmol/L or hypotension (systolic blood pressure <90 mm Hg) requiring vasopressor support, were enrolled. A control group of 30 patients presenting to the emergency department with minor emergencies was also enrolled.InterventionsThere were no interventions.Measurements and Main ResultsPlasma thiamine levels were measured at 0, 24, 48, 72, and 162 hours for patients in the study group. Absolute TD was defined as less than or equal to 9 nmol/L derived from established abnormal ranges per Quest laboratory. In the study group, 3 (10%) of 30 had absolute TD upon presentation; and an additional 3 patients (6/30, 20%) developed TD within 72 hours. None of the 30 controls (0/30, 0%) exhibited absolute TD. Of the vasopressor-dependent population, 7.7% (2/26) displayed TD on presentation. For the group overall, there was no correlation between thiamine and lactic acidosis. However, in patients without liver dysfunction, thiamine was statistically significantly negatively correlated with lactic acidosis (r = ?.50; P = .02). The relationship between thiamine and lactic acidosis held after multivariable regression analysis controlling for age, sex, and comorbid disease (P < .02).ConclusionsThese preliminary findings indicate that critically ill patients may present with TD or develop this deficiency during their acute illness. We also identified a potential association between thiamine levels and lactic acidosis in patients without significant liver injury.     

Procalcitonin and the role of biomarkers in the diagnosis and management of sepsis

Sepsis and severe sepsis cause significant morbidity and mortality among populations worldwide; the rapid diagnosis poses a considerable challenge to physicians in acute care settings. An ideal biomarker should allow, with high diagnostic accuracy, for an early and rapid recognition of sepsis. Procalcitonin (PCT) is a recently rediscovered biomarker that fulfills many of these requirements, especially in comparison to "older" and commonly used biomarkers, and that has demonstrated superior diagnostic accuracy for a variety of infections, including sepsis. While blood cultures are still considered the "gold standard" for the diagnosis of bacteremia and sepsis, and are perhaps one of the most important functions of the clinical microbiology laboratory, PCT provides important information in early stages of sepsis as well as during antimicrobial treatment. In fact, PCT can be useful for antimicrobial stewardship and its utilization may safely lead to significant reduction of unnecessary antimicrobial therapy. However, PCT is also less than a universal and perfect biomarker, as it can also be increased in noninfectious disease conditions. Laboratories and clinicians must appreciate the complexity of diagnostic algorithms for sepsis and understand the particular information that biomarkers, such as PCT, can offer. In that context, it is necessary to not only recognize the importance of critical clinical awareness and thorough physical patient examination, but also to understand traditional microbiological methods and the need for highly sensitive biomarker assays in order to facilitate an early diagnosis and goal-directed therapy in patients suspected of sepsis. This review is intended to provide additional information for clinicians and microbiologists to better understand the physiology and diagnostic utility of procalcitonin for sepsis and other infectious disease conditions.     

Procollagen type III aminoterminal propeptide as biomarker of host response in severe sepsis

Purpose

The purpose of this study is to test the hypothesis that procollagen type III aminoterminal propeptide (PIIINP) is early elevated in septic episodes and can indicate the acute organ dysfunction/failure characterizing severe sepsis.

Materials and Methods

This prospective study included 107 consecutive septic patients (44 with sepsis, 13 with severe sepsis, and 50 with septic shock) and 45 controls. After blood sampling (within 48 hours after onset of septic episodes), serum was assayed. Patients were followed up, and their disease severity was daily evaluated.

Results

Procollagen type III aminoterminal propeptide (median [range]) increased in patients with sepsis (9.4 [2.2-42.4] ng/mL) compared with controls (3.6 [1.9-4.9] ng/mL; P < .001), exhibiting further significant increase in patients with severe sepsis and septic shock (19.5 [6.0-52.4] and 20.2 [1.8-89.2] ng/mL, respectively; P < .01-.001 vs sepsis). Among biomarkers of host response severity, PIIINP was the sole that was independently associated with severe sepsis/septic shock (P = .01). The area under the receiver operating characteristic curve for PIIINP to predict which patients with sepsis would eventually develop severe sepsis/septic shock was 0.87; the cutoff of 12 ng/mL had sensitivity 82% and specificity 89%.

Conclusions

Increased serum PIIINP can signify severe sepsis/septic shock and predict which patients with sepsis will eventually develop severe sepsis/septic shock, thus representing a biomarker of risk stratification of patients with sepsis.     

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock

Objective To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis.Design The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A–E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management.Participants Participants included 44 critical care and infectious disease experts representing 11 international organizations.Results A total of 46 recommendations plus pediatric management considerations.Conclusions Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.Electronic Supplementary Material Supplementary material is available in the online version of this articel at This article is published jointly with Critical Care MedicineChairs: R. Phillip Dellinger, MD*; Henry Masur, MD; Jean M. Carlet, MD; Herwig Gerlach, MD, PhD**. Committee members: Richard J. Beale, MD**; Marc Bonten, MD; Christian Brun-Buisson, MD; Thierry Calandra, MD; Joseph A. Carcillo, MD; Jonathan Cohen, MD**; Catherine Cordonnier, MD; E. Patchen Dellinger, MD; Jean-Francois Dhainaut, MD, PhD; Roger G. Finch, MD; Simon Finfer, MD; Francois A. Fourrier, MD; Juan Gea-Banacloche MD; Maurene A. Harvey, RN, MPH**; Jan A. Hazelzet, MD; Steven M. Hollenberg, MD; James H. Jorgensen, PhD; Didier Keh, MD; Mitchell M. Levy*, MD; Ronald V. Maier, MD; Dennis G. Maki, MD; John J. Marini, MD; John C. Marshall, MD; Steven M. Opal, MD; Tiffany M. Osborn, MD; Margaret M. Parker, MD**; Joseph E. Parrillo, MD; Graham Ramsay, MD*; Andrew Rhodes, MD; Jonathan E. Sevransky, MD; Charles L. Sprung, MD, JD**; Antoni Torres, MD; Jeffery S. Vender, MD; Jean-Louis Vincent, MD, PhD**; Janice L. Zimmerman, MD. Associate members: E. David Bennett, MD; Pierre-Yves Bochud, MD; Alain Cariou, MD; Glenn S. Murphy, MD; Martin Nitsun, MD; Joseph W. Szokol, MD; Stephen Trzeciak, MD; Christophe Vinsonneau, MD. *Executive Committee, Surviving Sepsis Campaign. **Steering Committee, Surviving Sepsis Campaign.Sponsoring organizations: American Association of Critical-Care Nurses; American College of Chest Physicians; American College of Emergency Physicians; American Thoracic Society; Australian and New Zealand Intensive Care Society; European Society of Clinical Microbiology and Infectious Diseases; European Society of Intensive Care Medicine; European Respiratory Society; International Sepsis Forum; Society of Critical Care Medicine; Surgical Infection Society.The Surviving Sepsis Campaign is administered jointly by the European Society of Intensive Care Medicine, International Sepsis Forum, and the Society of Critical Care Medicine, and is supported in part by unrestricted educational grants from Baxter Bioscience, Edwards Lifesciences, and Eli Lilly and Company (majority sponsor).The authors and the publisher have exercised great care to ensure that drug dosages, formulas, and other information presented in this book are accurate and in accord with the professional standards in effect at the time of publication. Readers are, however, advised to always check the manufacturers product information sheet that is packaged with the respective products to be fully informed of changes in recommended dosages, contraindications, and the like before prescribing or administering any drug.     

Microcirculatory dysfunction in sepsis

Septic shock is a common and deadly disease that traditionally has been diagnosed and treated by evaluation and optimization of global hemodynamic indices. However, microcirculatory dysfunction is a critically important element in the pathophysiology of this disease. New techniques of in vivo video microscopy permit the assessment of microcirculatory function in human subjects. With the advent of these techniques, the microcirculation may represent a new frontier for developing novel therapies for sepsis.     

Oxidative stress and antioxidant status in prostate cancer patients: Relation to Gleason score, treatment and bone metastasis

Over the last decade, epidemiological, experimental and clinical studies have implicated oxidative stress in the development and progression of prostate cancer. In the present study, we evaluated the oxidative status and antioxidant defense in patients with prostate cancer (PCa) taking into consideration: treatment, Gleason score and bone metastasis. For this, we measured concentrations of plasmatic thiobarbituric acid reactive substances (TBARS), serum protein carbonylation, whole blood catalase (CAT) and superoxide dismutase (SOD) activities, as well as the plasma and erythrocyte thiol levels and serum vitamin C and E concentration. This study was performed on 55 patients with PCa and 55 healthy men. TBARS levels and serum protein carbonylation were higher in PCa patients than in controls and altered levels of antioxidants were found in these patients. CAT activity was decreased and SOD activity was higher in PCa patients when compared with controls. Non-protein thiol levels were increased, however, serum vitamin C and vitamin E content were reduced in PCa patients when compared with controls. In addition, different parameters analyzed in PCa patients based on metastasis, treatment and Gleason score showed changes in oxidative stress biomarkers and antioxidant defenses. These findings may indicate an imbalance in the oxidant/antioxidant status, supporting the idea that oxidative stress plays a role in PCa, moreover, the oxidative profile appear to be modified by bone metastasis, treatment and Gleason score.     

血清肝素结合蛋白在脓毒症患者中的表达与临床意义

目的：探讨血清肝素结合蛋白（HBP）在脓毒症时的表达水平及其临床意义。方法采用前瞻性研究方法,选择2011年2月至2014年4月江苏省中医院重症医学科确诊的各种原因引起的90例脓毒症患者为研究对象。按国际脓毒症指南将90例患者分为一般脓毒症组（26例）、严重脓毒症组（29例）和脓毒性休克组（35例）;按28 d预后将患者分为存活组（73例）和死亡组（17例）。另选择本院30例健康体检者作为健康对照组。采用酶联免疫吸附试验（ELISA）检测各组受试者血清HBP水平;同时检测各组受试者血中降钙素原（PCT）、白细胞计数（WBC）、血浆乳酸（Lac）水平和急性生理学与慢性健康状况评分系统Ⅱ（APACHEⅡ）评分。结果一般脓毒症组、严重脓毒症组、脓毒性休克组HBP、PCT、WBC、Lac均较健康对照组明显升高,且脓毒性休克组、严重脓毒症组上述各指标升高程度较一般脓毒症组更显著〔HBP（μg/L）：61.7±12.5、25.1±4.9比24.4±3.8,PCT（μg/L）：32.3±6.4、31.5±5.7比25.5±3.9,WBC（×109/L）：30.8±3.7、28.1±4.2比15.6±3.6, Lac（mmol/L）：11.6±3.7、8.7±3.6比5.8±3.8,均P＜0.05〕;脓毒性休克组与严重脓毒症组APACHEⅡ评分均明显高于一般脓毒症组（分：22.0±6.8、19.2±7.1比12.4±3.9,均P＜0.05）;脓毒性休克组HBP明显高于脓毒症组;脓毒性休克组与严重脓毒症组PCT、WBC、Lac、APACHEⅡ评分比较差异均无统计学意义（均P＞0.05）;不同器官功能障碍数患者血清HBP水平比较差异均无统计学意义〔器官功能障碍1、2、3、4、5个的患者HBP水平（μg/L）分别为19.6±7.9、27.5±5.3、32.0±3.6、20.5±5.8、24.8±4.1〕;死亡组血清HBP水平明显高于存活组（μg/L：101.4±16.2比27.3±4.8,P＜0.01）。结论血清HBP是预测脓毒症发生休克和早期死亡较好的特异性指标,但与发生器官功能障碍数无显著相关性。     

Current role of high dose vitamin C in sepsis management: A concise review

Sepsis and septic shock are common diagnoses for patients requiring intensive care unit admission and associated with high morbidity and mortality. In addition to aggressive fluid resuscitation and antibiotic therapy, several other drugs have been tried as adjuvant therapies to reduce the inflammatory response and improve outcomes. Vitamin C has been shown to have several biological actions, including anti-inflammatory and immunomodulatory effects, which may prove beneficial in sepsis management. Initial trials showed improved patient outcomes when high dose vitamin C was used in combination with thiamine and hydrocortisone. These results, along with relative safety of high-dose (supra-physiological) vitamin C, encouraged physicians across the globe to add vitamin C as an adjuvant therapy in the management of sepsis. However, subsequent large-scale randomised control trials could not replicate these results, leaving the world divided regarding the role of vitamin C in sepsis management. Here, we discuss the rationale, safety profile, and the current clinical evidence for the use of high-dose vitamin C in the management of sepsis and septic shock.     

Incidence and risk factors for sepsis in surgical patients: a cohort study

Purpose

The aim of the study was to evaluate risk factors for infection and sepsis in surgical patients admitted to the intensive care unit (ICU).

Materials and Methods

Data were prospectively collected from a cohort of surgical patients from January 2005 to December 2007. We analyzed the incidence of infection and sepsis and certain other variables from the pre-, intra-, and postoperative periods as risk factors for infection and sepsis.

Results

We studied 625 surgical patients. The mortality rate was 18.2%, and the mean age of the subjects was 53.1 ± 18.8 years. The incidences of severe sepsis and septic shock were 5% and 11.5%, respectively. A multivariate analysis showed that the following variables were associated with sepsis in the postoperative period: urgent surgery (odds ratio, 2.63; 95% confidence interval [CI], 1.50-4.63), fluid resuscitation (odds ratio, 1.90; 95% CI, 1.18-3.05), vasoactive drugs (odds ratio, 2.58; 95% CI, 1.61-4.14), and mechanical ventilation (odds ratio, 5.51; 95% CI, 3.07-9.89). A Sequential Organ Failure Assessment was associated with infection or sepsis upon ICU admission (area under the curve, 0.737 ± 0.019; 95% CI, 0.748-0.825).

Conclusions

This study showed that sepsis has high incidence and mortality in surgical patients admitted to the ICU. Urgent surgeries, mechanical ventilation, fluid resuscitation, and vasoactive drugs in the postoperative period and Sequential Organ Failure Assessment at ICU admission were risk factors for sepsis.     

Protein carbonyls as a biomarker of foetal-neonatal hypoxic stress

Objectives:

Investigation of the effect of hypoxic conditions during labour on the protein oxidative modifications and changes in plasma antioxidative capacity of newborns.

Design and methods:

Oxidative damage to proteins was determined by high-performance liquid chromatography. Antioxidative status was monitored by Trolox equivalent antioxidant capacity method. In our study, 11 hypoxic and 19 normoxic newborns were involved.

Results:

In hypoxic newborns, we have found a significant increase in protein carbonyl levels (3.55 ± 0.86 versus 3.24 ± 0.69 mol carbonyls/mol proteins, p = 0.045) and plasma antioxidant capacity (1.76 ± 0.056 versus 1.68 ± 0.097 mmol Trolox/L, p = 0.004) when compared to normoxic children. Bilirubin levels were unchanged (p = 0.87).

Conclusion:

Our results show elevated levels of carbonyls in hypoxic neonates compared to normoxic children. The oxidative damage to proteins is not sufficiently prevented by increased antioxidant capacity detected in plasma of hypoxic newborns.     

Neopterin as a prognostic biomarker in intensive care unit patients

Purpose

The present study was undertaken to evaluate urinary neopterin in intensive care unit patients.

Materials and Methods

Urinary neopterin levels were determined in systemic inflammatory response syndrome (n = 10), sepsis (n = 18), septic shock (n = 9), and multiple organ dysfunction syndrome (n = 5). It was tested whether neopterin is a differential parameter among the patient groups. Furthermore, the results were also evaluated by comparing with a healthy control group (n = 30), and the relationship between neopterin and mortality or Acute Physiology and Chronic Health Evaluation II scores were investigated.

Results

Neopterin levels of the control group and patients were detected as 111 ± 11 and 3850 ± 1081 μmol/mol creatinine, respectively (P < .05). It was significantly increased in the sepsis and septic shock groups compared to the systemic inflammatory response syndrome group (P < .05). Neopterin levels were significantly higher in the patients with mortality and lower Acute Physiology and Chronic Health Evaluation II scores.

Conclusion

This study showed that monitoring of urinary neopterin profile can be used in intensive care units to show the degree and prognosis of the disease.     

Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008

Objective To provide an update to the original Surviving Sepsis Campaign clinical management guidelines, “Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock,” published in 2004. Design Modified Delphi method with a consensus conference of 55 international experts, several subsequent meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. This process was conducted independently of any industry funding. Methods We used the GRADE system to guide assessment of quality of evidence from high (A) to very low (D) and to determine the strength of recommendations. A strong recommendation [1] indicates that an intervention's desirable effects clearly outweigh its undesirable effects (risk, burden, cost), or clearly do not. Weak recommendations [2] indicate that the tradeoff between desirable and undesirable effects is less clear. The grade of strong or weak is considered of greater clinical importance than a difference in letter level of quality of evidence. In areas without complete agreement, a formal process of resolution was developed and applied. Recommendations are grouped into those directly targeting severe sepsis, recommendations targeting general care of the critically ill patient that are considered high priority in severe sepsis, and pediatric considerations. Results Key recommendations, listed by category, include: early goal-directed resuscitation of the septic patient during the first 6 hrs after recognition (1C); blood cultures prior to antibiotic therapy (1C); imaging studies performed promptly to confirm potential source of infection (1C); administration of broad-spectrum antibiotic therapy within 1 hr of diagnosis of septic shock (1B) and severe sepsis without septic shock (1D); reassessment of antibiotic therapy with microbiology and clinical data to narrow coverage, when appropriate (1C); a usual 7–10 days of antibiotic therapy guided by clinical response (1D); source control with attention to the balance of risks and benefits of the chosen method (1C); administration of either crystalloid or colloid fluid resuscitation (1B); fluid challenge to restore mean circulating filling pressure (1C); reduction in rate of fluid administration with rising filing pressures and no improvement in tissue perfusion (1D); vasopressor preference for norepinephrine or dopamine to maintain an initial target of mean arterial pressure ≥ 65 mm Hg (1C); dobutamine inotropic therapy when cardiac output remains low despite fluid resuscitation and combined inotropic/vasopressor therapy (1C); stress-dose steroid therapy given only in septic shock after blood pressure is identified to be poorly responsive to fluid and vasopressor therapy (2C); recombinant activated protein C in patients with severe sepsis and clinical assessment of high risk for death (2B except 2C for post-operative patients). In the absence of tissue hypoperfusion, coronary artery disease, or acute hemorrhage, target a hemoglobin of 7–9 g/dL (1B); a low tidal volume (1B) and limitation of inspiratory plateau pressure strategy (1C) for acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); application of at least a minimal amount of positive end-expiratory pressure in acute lung injury (1C); head of bed elevation in mechanically ventilated patients unless contraindicated (1B); avoiding routine use of pulmonary artery catheters in ALI/ARDS (1A); to decrease days of mechanical ventilation and ICU length of stay, a conservative fluid strategy for patients with established ALI/ARDS who are not in shock (1C); protocols for weaning and sedation/analgesia (1B); using either intermittent bolus sedation or continuous infusion sedation with daily interruptions or lightening (1B); avoidance of neuromuscular blockers, if at all possible (1B); institution of glycemic control (1B) targeting a blood glucose < 150 mg/dL after initial stabilization ( 2C ); equivalency of continuous veno-veno hemofiltration or intermittent hemodialysis (2B); prophylaxis for deep vein thrombosis (1A); use of stress ulcer prophylaxis to prevent upper GI bleeding using H2 blockers (1A) or proton pump inhibitors (1B); and consideration of limitation of support where appropriate (1D). Recommendations specific to pediatric severe sepsis include: greater use of physical examination therapeutic end points (2C); dopamine as the first drug of choice for hypotension (2C); steroids only in children with suspected or proven adrenal insufficiency (2C); a recommendation against the use of recombinant activated protein C in children (1B). Conclusion There was strong agreement among a large cohort of international experts regarding many level 1 recommendations for the best current care of patients with severe sepsis. Evidenced-based recommendations regarding the acute management of sepsis and septic shock are the first step toward improved outcomes for this important group of critically ill patients. Sponsoring Organizations: American Association of Critical-Care Nurses*, American College of Chest Physicians*, American College of Emergency Physicians*, Canadian Critical Care Society, European Society of Clinical Microbiology and Infectious Diseases*, European Society of Intensive Care Medicine*, European Respiratory Society*, International Sepsis Forum*, Japanese Association for Acute Medicine, Japanese Society of Intensive Care Medicine, Society of Critical Care Medicine*, Society of Hospital Medicine**, Surgical Infection Society*, World Federation of Societies of Intensive and Critical Care Medicine**. Participation and endorsement by the German Sepsis Society and the Latin American Sepsis Institute. for the International Surviving Sepsis Campaign Guidelines Committee***, **** * Sponsor of 2004 guidelines; ** Sponsor of 2008 guidelines but did not participate formally in revision process; *** Members of the 2007 SSC Guidelines Committee are listed in Appendix I.; **** Please see Appendix J for author disclosure information. The article will also be published in Critical Care Medicine. An erratum to this article can be found at     

脓毒症氧化应激与抗氧化治疗研究进展

脓毒症(sepsis)是感染引起的全身炎性反应综合征,是急危重患者的严重并发症之一。氧化应激是机体活性氧簇和活性氮簇产生过多或清除能力下降,导致潜在性损伤的病理过程。氧化应激在脓毒症发生、发展中发挥重要作用,早期进行抗氧化干预可能有益于脓毒症防治。丙酮酸乙酯(ethyl pyruvate,EP)是一种稳定的丙酮酸酯类衍生物,它对于发生急性损伤的器官具有显著的保护作用。本文就脓毒症氧化应激与丙酮酸乙酯抗氧化治疗的最新进展作一综述。