Guidelines For Management Of Sepsis Research Articles

Part III: Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS) for Fluid Resuscitation and Antimicrobial Therapy Endpoints.

As outlined in the "International Guidelines for Management of Sepsis and Septic Shock: 2016," initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part III report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen (s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

An observational study of the effects of a clinical nurse specialist quality improvement project for clinical reminders for sepsis on patient outcomes and nurse actions

Background: Clinicalreminders (CRs) are designed to cue the healthcare team to provideevidence-based guidelines and care. Inappropriate, delayed, or lack of responseto CRs for sepsis may result in excessive reminders contributing to alarmfatigue and failure to rescue. Methods: QualitativeInitiative/Analysis, Retrospective Medical Review, Questionnaire/Survey.Pre/post data pull (audit) of the impact of the study interventions (editingthe CRs, updating nurse and physician on latest sepsis guidelines).Post-intervention survey of nurses/clinicians regarding their response to CRs.Specific aims: (I) improve sepsis bundle compliance using Sepsis CMS CoreMeasure (SEP-1) criteria; (II) increase efficiency of CR/best practice alerts(BPAs) by decreasing frequency of inappropriate CR/BPAs via refinement ofresponse algorithm; (III) provide nurse/clinician update of Surviving SepsisCampaign (SSC): International Guidelines for Management of Sepsis and SepticShock: 2016. Results: Theinstitution’s inpatient hospital quality measures dashboard: sepsis: earlymanagement bundle, severe sepsis/septic shock: sampled. Centers for Medicare& Medicaid Services (CMS). Pre-project adherence (July 2017) =3%;post-project adherence (December 2017) =48% positive trending to nearinstitutional goal with a 45% improvement with adherence to the sepsis bundle(institutional target ≥50%). Inpatient optimalcare reported via The Balanced Scorecard—hospital core measure: inpatientoptimal care score: sepsis (SEP-1) demonstrated a 94.85% increase in YTD 18 Actual41.7% compared to YTD 17 Actual 21.4% (data source—Quantros). #CR/BPA pre- andpost-intervention—base sepsis detection/SIRS criteria for registered nurse (RN)(sepsis CR/BPA) July 2017—13,391 (pre-intervention) compared to January2018—16,612 (post-intervention) (February 2018—11,081) and July 2018—8,622 (6months later). The nursing survey revealed nursing documentation practice canaffect timing of CRs and potentially delay recognition of sepsis/septic shock.Protocols for sepsis being in place does not equate to adherence to policy. Conclusions: Reminderfatigue is a not completely unavoidable with increasingly complex patients. CRdesign, education for use, and continued auditing can decrease alarm fatigueand improve patient outcomes.

Implementation of guidelines for sepsis management in emergency departments: A systematic review

IntroductionTimely, evidence-based emergency care for sepsis saves lives. The primary aim of this systematic review was to examine the effect of implementation of guidelines for the ED management of sepsis on time to antibiotic administration. Secondary aims were to examine changes in evidence-based sepsis care and patient outcomes. MethodIn August 2018, we performed a systematic literature review of English language publications from 1st January 2002 and 31st July 2018 indexed in a number of academic databases using search terms related to sepsis, emergency care, guidelines and evidence-based practice. ResultsTwenty-four studies were included for analysis: all used longitudinal repeated-measures cohort study designs. The studies were of low-to-moderate methodological quality. Of the 24 studies included, 22 (92%) reported decreases in antibiotic administration times and two (8%) reported an increase in antibiotic administration time. All eight studies measuring compliance to completing all components of the sepsis guidelines, as well as all 12 studies measuring lactate sampling reported improvements in antibiotic administration times. Reductions in inpatient mortality ranging from 0.8% to 30.4% were reported in 12 studies and two studies reported increases. ConclusionImplementation of local sepsis management guidelines in EDs improves the timeliness of processes of care and may improve patient outcomes.

SOMANZ Guidelines for the Investigation and Management of Sepsis in Pregnancy

(Aust N Z J Obstet Gynaecol 2017;57:540–551) Sepsis, caused by Group A beta hemolytic streptococcal (GAS) infection, is an increasing cause of maternal mortality in both Australia and the United Kingdom. Sepsis can lead to insufficiency in maternal circulation, leading to compromised fetal perfusion and fetal distress. The Society of Obstetric Medicine of Australia and New Zealand (SOMANZ) has designed evidence-based guidelines for the effective investigation and management of sepsis in pregnant and postpartum women.

A survey report on use of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016

A survey report on use of the Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016

Abstract P-209: IMPACT INTERNATIONAL GUIDELINES MANAGEMENT OF SEVERE SEPSIS /SEPTIC SHOCK ON MORTALITY REDUCTION DUE TO SEPTIC SHOCK IN PICU IN CENTRAL AMERICA, A 10 YR FOLLOW-UP.

Aims & Objectives: The International Guidelines for Management of Severe Sepsis and Septic Shock published in 2008 and updated in 2016 represent a milestone for the mortality rate reduction due to infectious origin shock. Methods Pediatric Critical Care Unit (PICU) of a High Concentration Hospital, a 10 year follow-up of the mortality rate was performed. The admitted patients with shock diagnosis in the PICU between 2006 and 2016 were evaluated. n=268 subjects, medium age 13.7 months (±27.8 months). The identified shock types included: anaphylactic (0.4%), cardiogenic (0.7%), hypovolemic (8.6%), spinal (0.4%) and septic (89.9%). Results From 2006 and 2016 and since the systematic use of the Guidelines, it was observed a 40% percent reduction in the mortality rate; also it was observed that the risk of death in the subjects under 1 year old considered as a risk group, it is not higher than the subjects over 1 year old since the introduction of those guidelines (p=0.49). A reduction in the number of deaths due to septic shock was also observed; there were not significant statistical differences between the numbers of deaths due to septic shock when it is compared with the numbers of deaths due to shock with other causes. Conclusions Systematic and supervised implementation of validated guidelines for the sepsis and septic shock management can reduce the mortality rate due to these causes, representing a fundamental tool for the pediatric critical care units.

685 - Time to Antibiotics: An EBP Project to Improve the Time of Antibiotic Administration after a Neutropenic Patient Develops a New Onset Fever

Topic Significance & Study Purpose/Background/Rationale: According to the “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock” (2013), it is recommended that the administration of effective intravenous antimicrobials within the first hour of recognition of septic shock and severe sepsis without septic shock should be the goal of therapy. The data from January, 2015, through September, 2016, showed that 27 transplant patients experienced new onset fever during their SCT admission. Out of those 27 patients, only 12 had antibiotics initiated within 60 minutes of the newly onset fever (44%), and 15 had antibiotics initiated in greater than 60 minutes (56%), with an average time of 71 minutes. In order to improve patient care and impact outcomes, a standard process needed to be developed and implemented to meet the recommended goal of antibiotic administration within 60 minutes of fever. Methods, Intervention, & Analysis: The proposed practice change was the addition of a PRN antibiotic order to the SCT supportive care order set. The conditions of the order included fever definition, blood cultures to be obtained prior to administration, and provider notification. The bedside RN was then responsible for calling pharmacy when conditions were met and the dose was needed. Along with this practice change, an educational approach was directed to all healthcare professionals responsible for the care of these patients. Findings & Interpretation: After implementation of the PRN antibiotic order, data was collected from October, 2016, through September, 2017, showing that 25 patients experienced new onset fever during their SCT admission. Out of those 25 patients, 21 had antibiotics initiated within 60 minutes of the newly onset fever (84%), and 4 had antibiotics initiated in greater than 60 minutes (16%), with an average time of 46 minutes. Discussion & Implications: The addition of the PRN antibiotic order to the SCT supportive care order set, along with detailed education for healthcare professionals caring for these patients, greatly improved the time of antibiotic administration after fever to less than 60 minutes.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

Background and purposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 and published in the Journal of JSICM, [2017; Volume 24 (supplement 2)] https://doi.org/10.3918/jsicm.24S0001 and Journal of Japanese Association for Acute Medicine [2017; Volume 28, (supplement 1)] http://onlinelibrary.wiley.com/doi/10.1002/jja2.2017.28.issue-S1/issuetoc.This abridged English edition of the J-SSCG 2016 was produced with permission from the Japanese Association of Acute Medicine and the Japanese Society for Intensive Care Medicine.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ) and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two-thirds (> 66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J-SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation, and its supporting evidence were also added to each recommendation statement. We conducted meta-analyses for 29 CQs. Thirty-seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for five CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese-specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non-specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J-SSCG 2016).

Background and PurposeThe Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG 2016), a Japanese‐specific set of clinical practice guidelines for sepsis and septic shock created jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in February 2017 in Japanese. An English‐language version of these guidelines was created based on the contents of the original Japanese‐language version.MethodsMembers of the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine were selected and organized into 19 committee members and 52 working group members. The guidelines were prepared in accordance with the Medical Information Network Distribution Service (Minds) creation procedures. The Academic Guidelines Promotion Team was organized to oversee and provide academic support to the respective activities allocated to each Guideline Creation Team. To improve quality assurance and workflow transparency, a mutual peer review system was established, and discussions within each team were open to the public. Public comments were collected once after the initial formulation of a clinical question (CQ), and twice during the review of the final draft. Recommendations were determined to have been adopted after obtaining support from a two‐thirds (>66.6%) majority vote of each of the 19 committee members.ResultsA total of 87 CQs were selected among 19 clinical areas, including pediatric topics and several other important areas not covered in the first edition of the Japanese guidelines (J‐SSCG 2012). The approval rate obtained through committee voting, in addition to ratings of the strengths of the recommendation and its supporting evidence were also added to each recommendation statement. We conducted meta‐analyses for 29 CQs. Thirty seven CQs contained recommendations in the form of an expert consensus due to insufficient evidence. No recommendations were provided for 5 CQs.ConclusionsBased on the evidence gathered, we were able to formulate Japanese‐specific clinical practice guidelines that are tailored to the Japanese context in a highly transparent manner. These guidelines can easily be used not only by specialists, but also by non‐specialists, general clinicians, nurses, pharmacists, clinical engineers, and other healthcare professionals.

Percutaneous nephrostomy via the central venous catheter in combination with selective ureteroscopic lithotripsy for the treatment of ureteral stones in the middle-upper segment.

To explore the therapeutic outcome and significance of preoperative percutaneous nephrolithotomy (PCNL) via the central venous catheter in combination with two-step hard ureteroscopic lithotripsy for the treatment of ureteral stones in the middle-upper segment. The success rate and the occurrence of severe infection and perirenal hematoma were analyzed retrospectively in 37 patients who received preoperative PCNL via the central venous catheter in combination with two-step hard ureteroscopic lithotripsy for the treatment of ureteral stones in the middle-upper segment in our hospital between July 2012 and November 2014. The operation duration was 12-38 min with a mean of 18.5 min. The procedure was performed successfully in all patients without the postoperative occurrence of perirenal hematoma in any patient. No severe infection occurred in any patient according to the Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis (2012). Preoperative PCNL via the central venous catheter can significantly improve the success rate of ureteroscopic lithotripsy for the treatment of ureteral stones in the middle-upper segment, and reduce postoperative occurrences of severe infection and perirenal hematoma.

A Multicenter Survey of House Staff Knowledge About Sepsis and the "Surviving Sepsis Campaign Guidelines for Management of Severe Sepsis and Septic Shock".

We aimed to assess the knowledge, attitudes, and perceptions of resident physicians regarding sepsis in general and the Surviving Sepsis Campaign Guidelines in particular. After institutional review board approval, we surveyed internal medicine (IM) and emergency medicine (EM) house staff from 3 separate institutions. House staff were notified of the survey via e-mail from their residency director or chief resident. The survey was Internet-based (using http://www.surveymonkey.com ), voluntary, and anonymous. The Surviving Sepsis Campaign Guidelines were used to develop the survey. The survey was open between December 2015 and April 2016. No incentives for participation were given. Reminder e-mails were sent approximately every 3 to 4 weeks to all eligible participants. Comparisons of responses were evaluated using the N-1 2-proportion test. A total of 133 responses were received. These included 84 from IM house staff, 27 from EM house staff, and 22 who selected "other." Eighty (101/126) percent reported managing at least 1 patient with sepsis in the preceding 30 days, 85% (97/114) rated their knowledge of the Surviving Sepsis Guidelines as "very familiar" or at least "somewhat familiar," and 84% (91/108) believed their training in the diagnosis and management of sepsis was "excellent" or at least "good." However, 43% (47/108) reported not receiving any feedback on their treatment of patients with sepsis in the last 30 days, while 24% (26/108) received feedback once. Both IM and EM house staff received comparable rates of feedback (62% vs 48%, respectively; P = .21). For the 3 questions that directly tested knowledge of the guidelines, the scores of the IM and EM house staff were similar. Notably, <20% of both groups correctly identified diagnostic criteria for sepsis. Additional education of IM and EM house staff on the Surviving Sepsis Campaign Guidelines is warranted, along with more consistent feedback regarding their diagnosis and management of sepsis.

The diagnostics of sepsis in pregnant women and during postpartum period: the controversial questions of surviving sepsis campaign (International Guidelines for Management of Sepsis and Septic Shock), updated in 2016

Sepsis and septical shock clinical criteria were agreed in Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock 2016. Despite the imperfections of SIRS criteria (low specificity), their sensitivity reaches 100%. According to modern ideas, sepsis is a systemic inflammatory response to infection (Systemic Inflammatory Response Syndrome – SIRS) always associated with the presence of infectious agent in the body. Clinical and metabolical manifestations of sepsis are similar to symptoms and criteria of system inflammatory response syndrome. Physiological features of pregnant women are making adjustments to the classical picture of diagnosis and treatment. In the first trimester of pregnancy 15% of women are suffering from dyspnea. Increased heart rate is normal manifestation of the third mechanism of regulation of cardiac output (volume of circulating blood – first, the contractile ability of the myocardium – second). Increase in the number of leukocytes in peripheral blood of pregnant/postpartum women is a physiological process and creates difficulties in diagnostic process. The aim of study was to determine peculiarities of sepsis and septical shock in pregnant and postpartum women according to instructions of Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. The problem of sepsis is currently very severe in obstetrics. In now days, infections occupy third place in the structure of maternal mortality and make up about 15%. Systemic manifestations of sepsis/septical shock in pregnant/postpartum women (including the development of multiple organ dysfunction) can significantly outpace local changes of purulent source. If the primal source of infection is located in the uterus, the development of septical shock is not always accompanied by symptoms of “classical” metroendometritis, making it difficult to diagnose. It also detains radical sanation of the infectious source contributing to progression of multiple organ dysfunction. In 2001 E.P. Rivers et al. published an article in highly ranked journal N Eng J Med, which is cited by various authors until now. The whole algorithm of infusion and inotropic therapy was developed on its basis for patients with sepsis and septic shock. Despite this, in present time many authors doubt in expediency of achieving CVP 8-13 mmHg (J.H.Boyd et al 2011; M.Cessoni et al 2011; Marik P.E. et al 2008)., sodium ions accumulate in the extracellular space (interstitial and intravascular) in pregnant; as a result tissues become hydrophilic and tissue “phisiological edema” develops. Given the presence of capillary loss syndrome in pregnant/ postpartum women (preeclampsia / eclampsia) controversial is the question of the qualitative composition of the infusion therapy. There are no safe antibiotics for pregnant women according to Food and Drug Administration – FDA (USA). Therefore, the problem of antibiotic therapy in these patients also have its own features. Physiological features of pregnant woman are making adjustments to the classical picture of diagnosis and treatment of sepsis/septical shock in this group of patients. The aim of study was to determine peculiarities of sepsis and septical shock in pregnant and postpartum women according to instructions of Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. The problem of sepsis is currently very severe in obstetrics. In now days, infections occupy third place in the structure of maternal mortality and make up about 15%.In this article we have discussed the results of the diagnosis and treatment of 14 pregnant /postpar tum women with sepsis, who came to the clinic of anesthesiology and intensive care of the Lviv Regional Hospital from 2010 to 2016.Chorioamnionitis and endometritis were the main reasons of peritonitis and sepsis. Intensive therapy (volemic resuscitation, cardio-respiratory support, antibiotic therapy) and surgical intervention (eliminating the causes of peritonitis, sanitation and drainage of the abdominal cavity) were conducted to all the patients. The patient’s general condition was evaluated by APACHE II scale at 14,5 ± 1,5 points and multiple organ dysfunction was evaluated at 5,0 ± 1 points by SOFA scale.

Comparison of Procalcitonin and C-reactive Protein in Differential Diagnosis of Sepsis and Severe Sepsis in Emergency Department

Objective: Sepsis and severe sepsis (sepsis accompanied by acute organ dysfunction) are leading causes of death worldwide. In this study, our aim was to investigate utility of biomarkers commonly used in diagnosis of sepsis in discriminating these two entities. Methods: Two-hundred and three patients involved were divided into 2 subgroups as sepsis and severe sepsis according to Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2012. Then groups were compared according to clinical and laboratory (including C-reactive protein (CRP) and procalcitonin (PCT) levels) characteristics. Results: Of 203 patients included into the study, 124 (61.1%) were male and 79 (38.9%) were female. The most common reason for sepsis was urinary tract infection (n=64, 31.5%), followed by catheter infection (n=16, 7.9%) and pneumonia (n=14, 6.9%). Escherichia coli was the most common agent in both blood and urinary cultures. Majority of the patients were treated with ceftriaxone (n=33, 16.3%), followed by meronem/dapson (n=25, 12.3%). In both groups, CRP and PCT levels were high, even higher in severe sepsis group. However, any statistical significance could not be determined between groups. Mortality rate in sepsis patients was 6.4%. Conclusion: Plasma levels of both markers elevate in sepsis and severe sepsis. It was determined that CRP and PCT is higher in severe sepsis than in sepsis. However, the difference is not statistically significant. Plasma levels of CRP and PCT are not useful in differential diagnosis of sepsis and severe sepsis.

Interpretation of International Guidelines for Management of Sepsis and Septic Shock: 2016

国际专家组对拯救脓毒症运动：2012版脓毒症和脓毒性休克管理指南进行了更新，结果发表于Critical Care Medicine杂志。专家组提出了93条关于脓毒症和脓毒性休克早期管理及复苏的推荐意见。众多国际专家就脓毒症患者的最佳管理形成了较多强烈推荐意见。虽然有相当数量的推荐意见证据级别较弱，但以证据为基础的推荐意见用于脓毒症及脓毒性休克的早期管理是改善预后的基础。

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016.

To provide an update to "Surviving Sepsis Campaign Guidelines for Management of Sepsis and Septic Shock: 2012." A consensus committee of 55 international experts representing 25 international organizations was convened. Nominal groups were assembled at key international meetings (for those committee members attending the conference). A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. A stand-alone meeting was held for all panel members in December 2015. Teleconferences and electronic-based discussion among subgroups and among the entire committee served as an integral part of the development. The panel consisted of five sections: hemodynamics, infection, adjunctive therapies, metabolic, and ventilation. Population, intervention, comparison, and outcomes (PICO) questions were reviewed and updated as needed, and evidence profiles were generated. Each subgroup generated a list of questions, searched for best available evidence, and then followed the principles of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system to assess the quality of evidence from high to very low, and to formulate recommendations as strong or weak, or best practice statement when applicable. The Surviving Sepsis Guideline panel provided 93 statements on early management and resuscitation of patients with sepsis or septic shock. Overall, 32 were strong recommendations, 39 were weak recommendations, and 18 were best-practice statements. No recommendation was provided for four questions. Substantial agreement exists among a large cohort of international experts regarding many strong recommendations for the best care of patients with sepsis. Although a significant number of aspects of care have relatively weak support, evidence-based recommendations regarding the acute management of sepsis and septic shock are the foundation of improved outcomes for these critically ill patients with high mortality.

Venous-to-arterial carbon dioxide difference to arteriovenous oxygen content difference ratio combined with lactate to predict prognosis of patients with septic shock

To investigate the prognostic significance of venous-to-arterial carbon dioxide difference to arteriovenous oxygen content difference ratio (Pv-aCO2/Ca-vO2 ratio) combined with lactate in patients with septic shock during the early phases of resuscitation. A retrospective study was conducted for 104 septic shock patients. All patients received an initial fluid resuscitation according to the Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012(SSC2012). Patients were classified into four groups according to lactate levels and Pv-aCO2/Ca-vO2 ratio at 6 h of resuscitation: group A, lactate≥2.0 mmol/L and Pv-aCO2/Ca-vO2>1.0; group B, lactate≥2.0 mmol/L and Pv-aCO2/Ca-vO2≤1.0; group C, lactate<2.0 mmol/L and Pv-aCO2/Ca-vO2>1.0; group D, lactate<2.0 mmol/L and Pv-aCO2/Ca-vO2≤1.0. The hemodynamic parameters and oxygen metabolism parameters were recorded at baseline and 6 h after fluid resuscitation. Sequential organ failure assessment (SOFA) score at day 1, day 3 were calculated. The 28-day mortality rate was recorded. (1) Group A had the highest SOFA score at day 3 and group D the lowest, which were respectively 10.8±3.3, 6.7±3.6, 5.6±3.1, 4.1±2.2 in four groups. Accordingly, the 28-day mortality rate of group A was the highest and group D the lowest, which were respectively 83.3%, 59.1%, 60.0%, 14.3% in four groups. The differences were statistically significant (P<0.05). (2) The Cox regression analysis of 28 d mortality revealed that lactate levels (RR=4.306, 95%CI 1.979-9.369) and Pv-aCO2/Ca-vO2 ratio (RR=2.888, 95%CI 1.676-4.976) at T6 were independent predictors to 28-day mortality. (3) The AUCROC of Pv-aCO2/Ca-vO2 ratio combined with lactate [0.910(95%CI 0.857-0.963)] was significantly greater than the AUCROC of wither lactate [0.762(95%CI 0.673-0.852), Z=2.775; P=0.006) or Pv-aCO2/Ca-vO2 ratio [0.781(95%CI 0.693-0.868), Z=2.458; P=0.014) alone. Combination of Pv-aCO2/Ca-vO2 ratio and lactate level at early stage of resuscitation in patients with septic shock is better than single parameter to predict the prognosis.

The organ protective effects and timing of continuous blood purification in the treatment of severe sepsis：a double-blind randomized controlled trial

To investigate the organ protective effects and the timing of continuous blood purification (CBP) in the treatment of severe sepsis. A double-blind randomized controlled trial was conducted. Seventy-four patients with severe sepsis aged between 35 years and 80 years with acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) scores over 20 admitted to Department of Critical Care Medicine of the First Hospital of Wuhan from January 2013 to January 2015 were enrolled. They were divided into control group (n = 37) and treatment group (n = 37) by random number table method. All patients in these two groups received conventional therapy following the guidelines for management of severe sepsis in 2012. In addition the patients in treatment group received continuous veno-venous hemofiltration (CVVH). The critical score, liver and kidney function indexes, etc., levels of pro-inflammatory cytokines in plasma and ultra filtrate before and 24, 48, and 72 hours after treatment, and the clinical picture 2 weeks after treatment in two groups were observed. APACHE Ⅱ scores, multiple organ dysfunction syndrome (MODS) scores, Murray scores of acute lung injury, and systemic inflammatory response syndrome (SIRS) scores of the patients of the above two groups were gradually declined after the treatment. The levels of white blood cell count (WBC), procalcitonin (PCT), lactate (Lac), tumor necrosis factor-α (TNF-α), interleukins (IL-6 and IL-8), and endotoxin gradually lowered. Levels of blood urea nitrogen (BUN), serum creatinine (SCr), alanine transaminase (ALT) and the oxygenation index (PaO2/FiO2) showed a tendency of lowering. There were statistically significant differences in scores of critical illness, WBC, PCT, Lac, pro-inflammatory cytokine, liver and kidney function indexes, etc. between treatment group and control group 48 hours after treatment (APACHE Ⅱ score: 15.5±4.7 vs. 20.3±5.3, MODS score: 4.6±1.4 vs. 7.3±2.2, Murray score: 1.4±0.5 vs. 1.7±0.6, SIRS score: 2.9±0.8 vs. 3.7±1.0, WBC (×109/L): 1.1±0.5 vs. 1.6±0.5, PCT (μg/L): 26.7±12.0 vs. 32.4±14.1, Lac (mmol/L): 7.6±2.2 vs. 9.3±2.8, TNF-α (μg/L): 96.3±17.4 vs. 153.4±24.2, IL-6 (μg/L): 146.8±20.6 vs. 213.8±29.2, IL-8 (μg/L): 287.1±43.6 vs. 354.5±56.2, endotoxin (kEU/L): 1.4±0.5 vs. 2.6±0.8, BUN (mmol/L): 8.7±3.6 vs. 18.5±6.4, SCr (μmol/L): 143±39 vs. 197±42, ALT (U/L): 141±27 vs. 183±34, PaO2/FiO2 (mmHg, 1 mmHg = 0.133 kPa): 150.3±45.4 vs. 124.7±32.1, all P < 0.05], and the difference was significant up to 72 hours. In the treatment group, TNF-α, IL-6, IL-8, and endotoxin could be decreased in the filtrate 24 hours and 48 hours after treatment and they correlated with the lowering tendency of their plasma levels. Compared with the control group, CVVH based on conventional treatment of severe sepsis could significantly reduce the incidence of MODS (10.8% vs. 29.7%, χ2 = 4.423, P = 0.038) and mortality (5.4% vs. 13.5%, χ2 = 4.674, P = 0.032), and remarkably shortened the duration of mechanical ventilation (days: 3.1±0.6 vs. 5.3±1.7, t = 2.103, P = 0.045), and the length of intensive care unit (ICU) stay (days: 8.5±1.7 vs. 13.2±2.4, t = 2.245, P = 0.042). Early CBP can decrease the level of pro-inflammatory cytokines, prevent MODS, and remarkably improve the prognosis of patients with severe sepsis.

Clinicopathologic, Immunohistochemical, and Ultrastructural Findings of a Fatal Case of Middle East Respiratory Syndrome Coronavirus Infection in the United Arab Emirates, April 2014

Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes an acute respiratory illness and is associated with a high case fatality rate; however, the pathogenesis of severe and fatal MERS-CoV infection is unknown. We describe the histopathologic, immunohistochemical, and ultrastructural findings from the first autopsy performed on a fatal case of MERS-CoV in the world, which was related to a hospital outbreak in the United Arab Emirates in April 2014. The main histopathologic finding in the lungs was diffuse alveolar damage. Evidence of chronic disease, including severe peripheral vascular disease, patchy cardiac fibrosis, and hepatic steatosis, was noted in the other organs. Double staining immunoassays that used anti–MERS-CoV antibodies paired with immunohistochemistry for cytokeratin and surfactant identified pneumocytes and epithelial syncytial cells as important targets of MERS-CoV antigen; double immunostaining with dipeptidyl peptidase 4 showed colocalization in scattered pneumocytes and syncytial cells. No evidence of extrapulmonary MERS-CoV antigens were detected, including the kidney. These results provide critical insights into the pathogenesis of MERS-CoV in humans.

Effects of Safflower Yellow on the Treatment of Severe Sepsis and Septic Shock: A Randomized Controlled Clinical Trial.

Objective. To evaluate the clinical effect of safflower yellow on the treatment of severe sepsis and septic shock. Methods. 85 patients with severe sepsis and septic shock were randomly selected to receive either therapy according to the international guidelines for management of severe sepsis and septic shock (Surviving Sepsis Campaign 2012) (control group, n = 45) or conventional therapy plus safflower yellow (study group, n = 40). The 28-day mortality and 28-day Kaplan-Meier survival curves were compared as primary outcomes. Results. The 28-day mortality from all causes and in-hospital mortality were significantly lower in the study group (50%, 17.5%) as compared to the control group (78.58%, 54.76%) (P = 0.007, all causes, P < 0.001, in-hospital), and the 28-day Kaplan-Meier survival curve was higher in the study group than in the control group (P = 0.008, all causes, P < 0.001, in-hospital, Log Rank). 72 hours after treatment, secondary outcomes including heart rate, leukocyte counts, lactate levels, and platelet counts of patients in the study group were ameliorated significantly as compared with the control group. Conclusion. This study offers a potential new strategy employing safflower yellow to more effectively treat patients with severe sepsis and septic shock. This trial is registered with identifier ChiCTR-TRC-14005196.