Development of metabolic and inflammatory mediator biomarker phenotyping for early diagnosis and triage of pediatric sepsis

IntroductionThe first steps in goal-directed therapy for sepsis are early diagnosis followed by appropriate triage. These steps are usually left to the physician’s judgment, as there is no accepted biomarker available. We aimed to determine biomarker phenotypes that differentiate children with sepsis who require intensive care from those who do not.MethodsWe conducted a prospective, observational nested cohort study at two pediatric intensive care units (PICUs) and one pediatric emergency department (ED). Children ages 2–17 years presenting to the PICU or ED with sepsis or presenting for procedural sedation to the ED were enrolled. We used the judgment of regional pediatric ED and PICU attending physicians as the standard to determine triage location (PICU or ED). We performed metabolic and inflammatory protein mediator profiling with serum and plasma samples, respectively, collected upon presentation, followed by multivariate statistical analysis.ResultsNinety-four PICU sepsis, 81 ED sepsis, and 63 ED control patients were included. Metabolomic profiling revealed clear separation of groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.89, area under the receiver operating characteristic curve (AUROC) of 0.96 (standard deviation [SD] 0.01), and predictive ability (Q²) of 0.60. Protein mediator profiling also showed clear separation of the groups, differentiating PICU sepsis from ED sepsis with accuracy of 0.78 and AUROC of 0.88 (SD 0.03). Combining metabolomic and protein mediator profiling improved the model (Q² =0.62), differentiating PICU sepsis from ED sepsis with accuracy of 0.87 and AUROC of 0.95 (SD 0.01). Separation of PICU sepsis or ED sepsis from ED controls was even more accurate. Prespecified age subgroups (2–5 years old and 6–17 years old) improved model accuracy minimally. Seventeen metabolites or protein mediators accounted for separation of PICU sepsis and ED sepsis with 95 % confidence.ConclusionsIn children ages 2–17 years, combining metabolomic and inflammatory protein mediator profiling early after presentation may differentiate children with sepsis requiring care in a PICU from children with or without sepsis safely cared for outside a PICU. This may aid in making triage decisions, particularly in an ED without pediatric expertise. This finding requires validation in an independent cohort.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-015-1026-2) contains supplementary material, which is available to authorized users.     

C-reactive protein as an indicator of resolution of sepsis in the intensive care unit

Objective To investigate the value of decreasing plasma C-reactive protein (CRP) concentrations as an indicator or resolution of microbiologically-proven sepsis.Design: Retrospective analysis of CRP concentrations measured during episodes of microbiologicallyproven sepsis. A receiver-operating characteristic (ROC) curve was used to assess the usefulness of CRP as a test for resolution of sepsis.Setting The intensive care unit (ICU) of a teaching hospital.Patients and participants: 32 episodes of microbiologically-proven sepsis occurring in 18 patients were followed from diagnosis until resolution.Measurements and results Daily routine observations and blood testing were performed prospectively. The daily presence or absence of systemic inflammatory response syndrome (SIRS) was prospectively determined according to standard definitions. Concentrations of CRP were analysed retrospectively once the patients had left the ICU. A decrease in CRP by 25% or more from the previous day's level was a good indicator of resolution of sepsis, with a sensitivity of 97%, specificity of 95% and predictive value of 97%. In 13 cases (46%), a decrease in CRP preceded clinical resolution of sepsis; this was more likely to occur in patients with less severe sepsis than in those with severe sepsis or septic shock.Conclusion Daily measurement of CRP is useful for monitoring the course of microbiologically-proven sepsis in ICU patients, and may be used to indicate successful treatment.     

The epidemiology of the systemic inflammatory response

Objective: To examine the incidence, risk factors, aetiologies and outcome of the various forms of the septic syndromes (the systemic inflammatory response syndrome [SIRS] sepsis, severe sepsis, and septic shock) and their relationships with infection.¶Design: Review of published cohort studies examining the epidemiology of the septic syndromes, with emphasis on intensive care unit (ICU) patients.¶Results: The prevalence of SIRS is very high, affecting one-third of all in-hospital patients, and > 50 % of all ICU patients; in surgical ICU patients, SIRS occurs in > 80 % patients. Trauma patients are at particularly high risk of SIRS, and most these patients do not have infection documented. The prevalence of infection and bacteraemia increases with the number of SIRS criteria met, and with increasing severity of the septic syndromes. About one-third of patients with SIRS have or evolve to sepsis. Sepsis may occur in approximately 25 % of ICU patients, and bacteraemic sepsis in 10 %. In such patients, sepsis evolves to severe sepsis in > 50 % of cases, whereas evolution to severe sepsis in non-ICU patients is about 25 %. Severe sepsis and septic shock occur in 2 %–3 % of ward patients and 10 %–15 % or more ICU patients, depending on the case-mix; 25 % of patients with severe sepsis have shock. There is a graded severity from SIRS to sepsis, severe sepsis and septic shock, with an associated 28-d mortality of approximately 10 %, 20 %, 20 %–40 %, and 40 %–60 %, respectively. Mortality rates are similar within each stage, whether infection is documented or not, and microbiological characteristics of infection do not substantially influence outcome, although the source of infection does. While about three of four deaths occur during the first months after sepsis, the septic syndromes significantly impact on long-term outcome, with an estimated 50 % reduction of life expectancy over the following five years. The major determinants of outcome, both short-term and long-term, of patients with sepsis are the severity of underlying diseases and comorbidities, the presence of shock and organ failures at onset of sepsis or evolving thereafter. It has been estimated that two-thirds of the overall mortality can be attributed to sepsis.¶Conclusions: The prevalence of sepsis in ICU patients is very high, and most patients have clinically or microbiologically documented infection, except in specific subset of patients. The prognosis of septic syndromes is related to underlying diseases and the severity of the inflammatory response and its sequelae, reflected in shock and organ dysfunction/failures.     

Manifold beneficial effects of acetyl salicylic acid and nonsteroidal anti-inflammatory drugs on sepsis

Introduction

Acetyl salicylic acid (ASA) and nonsteroidal anti-inflammatory drugs (NSAIDs) may have potential as adjunctive agents for sepsis.

Materials

This review considers the large body of literature that indicates a basis for sepsis therapy with ASA and suggests an agenda for future intervention studies in sepsis prevention and treatment. ASA and NSAIDs have beneficial effects in numerous experimental models of sepsis. Low doses of ASA of 100?mg/day or less trigger synthesis of lipoxins that are anti-inflammatory and aid in resolution of inflammation. Higher doses of ASA and NSAIDs act to reduce NF-κB stimulation and inhibit numerous septic pathways. While a previous randomised controlled trial of ibuprofen failed to show a reduction in mortality in sepsis, it did reduce clinical manifestations of sepsis. More recent observational studies have shown reduction in sepsis or acute lung injury leading to lower mortality in ICU patients treated with ASA.

Conclusions

Low-dose ASA appears to be beneficial in the prevention and treatment of sepsis and SIRS. If proven, this intervention would have a major, cost-effective impact on sepsis care.     

National estimates of severe sepsis in United States emergency departments

OBJECTIVE: The emergency department (ED) often serves as the first site for the recognition and treatment of patients with suspected severe sepsis. However, few evaluations of the national epidemiology and distribution of severe sepsis in the ED exist. We sought to determine national estimates of the number, timing, ED length of stay, and case distribution of patients presenting to the ED with suspected severe sepsis. DESIGN: Analysis of 2001-2004 ED data from the National Hospital Ambulatory Medical Care Survey. SETTING: National multistage probability sample of United States ED data. PATIENTS: Adult (age, >or=18 yrs) patients with suspected severe sepsis, defined as the concurrent presence of an infec-tion (ED International Classification of Diseases, 9th Revision; ICD-9) diagnosis of infection, or a triage temperature <96.8 degrees F or >or=100.4 degrees F) and organ dysfunction (ED ICD-9) diagnosis of organ dysfunction, intubation, or a triage systolic blood pressure 6 hrs in the ED. Of suspected severe sepsis patients, 20.6% presented to a low-volume ED (相似文献   

Elevated thrombopoietin in plasma of burned patients without and with sepsis enhances platelet activation

Summary.  Background:  Thrombopoietin (TPO) is a humoral growth factor that does not induce platelet aggregation per se , but enhances platelet activation in response to several agonists. Circulating levels of TPO are increased in patients with sepsis and are mainly related to sepsis severity. Objectives:  To investigate the potential contribution of elevated TPO levels in platelet activation during burn injury complicated or not by sepsis. Methods:  We studied 22 burned patients, 10 without and 12 with sepsis, and 10 healthy subjects. We measured plasma levels of TPO, as well as leukocyte-platelet binding and P-selectin expression. The priming activity of plasma from burned patients or healthy subjects on platelet aggregation and leukocyte-platelet binding, and the role of TPO in these effects were also studied in vitro . Results:  Burned patients without and with sepsis showed higher circulating TPO levels and increased monocyte-platelet binding compared with healthy subjects. Moreover, TPO levels, monocyte-platelet binding and P-selectin expression were significantly higher in burned patients with sepsis than in burned patients without sepsis. In vitro , plasma from burned patients without and with sepsis, but not from healthy subjects, primed platelet aggregation, monocyte-platelet binding and platelet P-selectin expression. The effect of plasma from burned patients with sepsis was significantly higher than that of plasma from burned patients without sepsis. An inhibitor of TPO prevented the priming effect of plasma from burned patients. Conclusions:  Increased TPO levels may enhance platelet activation during burn injury and sepsis, potentially participating in the pathogenesis of multi-organ failure in these diseases.     

Quality of life of survivors from severe sepsis and septic shock may be similar to that of others who survive critical illness

Introduction

The objective of the present study was to compare the health-related quality of life (HR-QoL) of survivors from severe sepsis and septic shock with HR-QoL in others who survived critical illness not involving sepsis.

Methods

From March 1997 to March 2001, adult patients in an eight-bed medical/surgical intensive care unit (ICU) of a tertiary care hospital admitted with severe sepsis or septic shock (sepsis group; n = 305) were enrolled and compared with patients admitted without sepsis (control group; n = 392). Patients younger than 18 years (n = 48) and those whose ICU stay was 1 day or less (n = 453) were excluded. In addition, patients exhibiting nonsevere sepsis on admission were excluded (n = 87). Finally, patients who developed nonsevere sepsis or severe sepsis/septic shock after admission were also excluded (n = 88).

Results

In-hospital mortality rates were 34% in the sepsis group and 26% in the control group. There were no differences in sex, age, main activity (work status), and previous health state between groups. Survivors in the sepsis group had a significantly higher Acute Physiology and Chronic Health Evaluation II score on admission (17 versus 12) and stayed significantly longer in the ICU. A follow-up appointment was held 6 months after ICU discharge, and an EQ-5D (EuroQol five-dimension) questionnaire was administered. A total of 104 sepsis survivors and 133 survivors in the control group answered the EQ-5D questionnaire. Sepsis survivors reported significantly fewer problems only in the anxiety/depression dimension. Although there were no significant differences in the other dimensions of the EQ-5D, there was a trend towards fewer problems being reported by sepsis survivors.

Conclusion

Evaluation using the EQ-5D at 6 months after ICU discharge indicated that survivors from severe sepsis and septic shock have a similar HR-QoL to that of survivors from critical illness admitted without sepsis.     

Procalcitonin for early diagnosis and differentiation of SIRS,sepsis, severe sepsis,and septic shock

Objective To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II). Design Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period. Patients and methods A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms. Results PCT values were highest in patients with septic shock (12.89±4.39 ng/ml;P<0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91±3.87 ng/ml vs 0.53±2.9 ng/ml;P<0.001, and 0.41±3.04 ng/ml;P<0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26±1.62, 16.09±2.06, and 17.42±1.72 points, respectively), but was significantly higher in patients with septic shock (29.27±1.35,P<0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock. Conclusions In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.     

The decrease of PKCalpha is associated with hepatic apoptosis at early and late phases of polymicrobial sepsis

The present study investigates the relationship between the PKC-alpha and hepatic apoptosis during sepsis. Cecal ligation and puncture- (CLP) induced animal model of polymicrobial sepsis was used, with early and late sepsis referring to those animals sacrificed at 9 and 18 h, respectively, after CLP. The expressions of PKCalpha and Bcl-2 family proteins as well as poly(ADP-ribose) polymerase (PARP) cleavage were quantified to evaluate the possible factors involved in the hepatic cell death during sepsis. The apoptosis of hepatocytes under septic condition or hepatocytes treated with PKCalpha antisense was evaluated by gel electrophoresis and/or flow cytometry after Annexin-V-Fluos and propidium iodide staining. The results indicated that (1) the protein expression of membrane-associated PKCalpha was decreased at early (P < 0.05) and late (P < 0.01) sepsis; (2) the protein expressions of Bcl-2 and Bcl-xL were decreased, whereas Bax expression was increased at late sepsis; (3) the percentage of PARP cleavage was increased at early (P < 0.05) and late (P < 0.01) sepsis; (4) severe DNA fragmentation was observed at late sepsis; (5) the apoptotic cell population was increased at early and late sepsis; and (6) the percentage of apoptotic cell population in PKCalpha antisense-treated cells was significantly higher than that in untreated cells. These results suggest that inactivation of PKCalpha may play an important role in modulating hepatic apoptosis during sepsis and the apoptosis is closely associated with the alterations of Bcl-2 family proteins.     

Triage of patients with fever: The Manchester triage system's predictive validity for sepsis or septic shock and seven-day mortality

ObjectiveUp to 15% of patients arrive in the emergency department suffering from fever. Triage is their first contact and is responsible for the stratification of patients according to the severity of the condition for which they are presenting at the emergency department. The aim of this study is to assess the predictive validity of the Manchester Triage System in patients with fever for sepsis or septic shock and seven-day mortality.MethodsThe sensitivity, specificity and negative predictive value of the Manchester Triage System was assessed by priority code allocation towards seven-day mortality and the diagnosis of sepsis or septic shock.ResultsA total of 3831 patients were evaluated in the emergency department for fever between 1 January 2017 and 30 June 2019. Of these, 1.9% were diagnosed with sepsis or septic shock. Using the Manchester Triage System to predict diagnosis of sepsis or septic shock provided a sensitivity of 88.7%, a specificity of 50.1% and a negative predictive value of 99.5%. For seven-day mortality, sensitivity was 44.4%, specificity was 92.3% and the negative predictive value was 99.3%.ConclusionThe Manchester Triage System has demonstrated high sensitivity and negative predictive value in patients with fever diagnosed with sepsis or septic shock. For patients with sepsis or septic shock one-third of cases with an incorrectly assigned priority code were caused by incorrect application of the Manchester Triage System.     

Predictors of early progression to severe sepsis or shock among emergency department patients with nonsevere sepsis

Background

Progression from nonsevere sepsis—i.e., sepsis without organ failure or shock—to severe sepsis or shock among emergency department (ED) patients has been associated with significant mortality. Early recognition in the ED of those who progress to severe sepsis or shock during their hospital course may improve patient outcomes. We sought to identify clinical, demographic, and laboratory parameters that predict progression to severe sepsis, septic shock, or death within 96 h of ED triage among patients with initial presentation of nonsevere sepsis.

Methods

This is a retrospective cohort of patients presenting to a single urban academic ED from November 2008 to October 2010. Patients aged 18 years or older who met criteria for sepsis and had a lactate level measured in the ED were included. Patients were excluded if they had any combination of the following: a systolic blood pressure <90 mmHg upon triage, an initial whole blood lactate level ≥4 mmol/L, or one or more of a set of predefined signs of organ dysfunction upon initial assessment. Disease progression was defined as the development of any combination of the aforementioned conditions, initiation of vasopressors, or death within 96 h of ED presentation. Data on predefined potential predictors of disease progression and outcome measures of disease progression were collected by a query of the electronic medical record and via chart review. Logistic regression was used to assess associations of potential predictor variables with a composite outcome measure of sepsis progression to organ failure, hypotension, or death.

Results

In this cohort of 582 ED patients with nonsevere sepsis, 108 (18.6 %) experienced disease progression. Initial serum albumin <3.5 mg/dL (OR 4.82; 95 % CI 2.40–9.69; p?<?0.01) and a diastolic blood pressure <52 mmHg at ED triage (OR 4.59; 95 % CI 1.57–13.39; p?<?0.01) were independently associated with disease progression to severe sepsis or shock within 96 h of ED presentation. There were no deaths within 96 h of ED presentation.

Conclusions

In our patient cohort, serum albumin <3.5 g/dL and an ED triage diastolic blood pressure <52 mmHg independently predict early progression to severe sepsis or shock among ED patients with presumed sepsis.

     

qSOFA Has Poor Sensitivity for Prehospital Identification of Severe Sepsis and Septic Shock

Objectives: Sepsis is a common and deadly disease process for which early recognition and intervention can significantly improve clinical outcomes. Despite this, sepsis remains underrecognized and therefore undertreated in the prehospital setting. Recent recommendations by the Society of Critical Care and European Society of Intensive Care Medicine advocate use of the qSOFA (quick Sequential [Sepsis-related] Organ Failure Assessment) score in non-ICU settings to screen for septic patients at greater risk for poor outcomes. Methods: We retrospectively evaluated the sensitivity and specificity of a prehospital qSOFA score ≥ 2 for prehospital identification of patients with severe sepsis or septic shock. Emergency Department (ED) patients with confirmed or suspected infection were classified as having infection without sepsis (n = 71), sepsis (n = 38), or severe sepsis/septic shock (n = 43), where designation of severe sepsis/septic shock required evidence of end-organ dysfunction, hypoperfusion (lactate > 2), or vasopressor requirement. Results: We found that a prehospital qSOFA score ≥ 2 was 16.3% sensitive (95% CI 6.8–30.7%) and 97.3% specific (95% CI 92.1–99.4%) for patients ultimately confirmed to have severe sepsis/septic shock in the ED. Adding an additional point to the prehospital qSOFA score for a pulse > 100, nursing home residence, age > 50, or reported fever increased the sensitivity to 58.1% (95% CI 42.1–73.0%) and decreased the specificity to 78.0% (95% CI 69.0–85.4%). During their ED stay, approximately two-thirds of patients meeting severe sepsis/septic shock criteria eventually met qSOFA criteria with a sensitivity of 67.4% (95% CI 51.5–80.9) and specificity of 86.2% (95% CI 78.3–92). Failure to meet qSOFA criteria prehospital was predominantly due to a systolic blood pressure and respiratory rate that did not yet meet predetermined thresholds. Conclusions: These findings suggest that the dynamic nature of sepsis can make sensitive detection difficult in the prehospital setting, although combining qSOFA with other clinical information (age, nursing home status, fever, and tachycardia) can identify more patients with sepsis who may benefit from time critical interventions.     

The usefulness of the semiquantitative procalcitonin test kit as a guideline for starting antibiotic administration

Objectives

The Surviving Sepsis Campaign has recommended that antibiotic therapy should be started within the first hour of recognizing severe sepsis. Procalcitonin has recently been proposed as a biomarker of bacterial infection, although the quantitative procalcitonin assay is often time consuming, and it is not always available in many emergency departments (EDs). Our aim is to evaluate usefulness of the semiquantitative procalcitonin fast kit as a guideline for starting antibiotic administration for patients with severe sepsis or septic shock that requires prompt antibiotic therapy in the ED.

Methods

We include those patients who were admitted to the ED and who were suspected of having infection. The procalcitonin concentration was determined by semiquantitative PCT-Q strips, and the points of the severity scoring system were calculated. The receiver operating characteristic curve was used to assess the diagnostic value of the PCT-Q strips to predict severe sepsis or septic shock.

Results

Of the 80 recruited patients, 33 patients were categorized as having severe sepsis or septic shock according to the definition. At a procalcitonin cutoff level of 2 ng/mL or greater, the sensitivity of the PCT-Q for detecting severe sepsis or septic shock was 93.94% and the specificity was 87.23. The receiver operating characteristic curve for PCT-Q to predict severe sepsis or septic shock had an area under the curve of 0.916.

Conclusion

PCT-Q is probably a fast, useful method for detecting severe sepsis in the ED, and it can be used as a guideline for antibiotic treatment.     

To be,or not to be immunocompetent

Several data support the view that impairment of the inflammatory-immune response is a hallmark of severe sepsis and the level and time of recovery to immunocompetence has a major impact on the clinical outcome of ICU patients. Recent studies demonstrate that improvement of anti-tumour immune response by targeting negative regulatory molecules, such as CD25, chronic T-lymphocyte activation antigen 4, and programmed death-1 receptor (PD-1)/PD-1 L, offers a novel opportunity to prevent or even reverse progression of tumour growth in experimental models and patients. Likewise, severe sepsis is associated with enhanced expression of those negative regulatory molecules, suggesting a novel approach to reverse immunoparalysis in sepsis. Consequently, targeting negative molecules in sepsis can reverse immunoparalysis and improve survival in experimental sepsis, as shown by Chang and colleagues in a recent issue of Critical Care. This opens new opportunities to overcome overwhelming downregulation of the adaptive immune response to prevent and/or improve recovery from sepsis.     

Renal blood flow in sepsis

Introduction

To assess changes in renal blood flow (RBF) in human and experimental sepsis, and to identify determinants of RBF.

Method

Using specific search terms we systematically interrogated two electronic reference libraries to identify experimental and human studies of sepsis and septic acute renal failure in which RBF was measured. In the retrieved studies, we assessed the influence of various factors on RBF during sepsis using statistical methods.

Results

We found no human studies in which RBF was measured with suitably accurate direct methods. Where it was measured in humans with sepsis, however, RBF was increased compared with normal. Of the 159 animal studies identified, 99 reported decreased RBF and 60 reported unchanged or increased RBF. The size of animal, technique of measurement, duration of measurement, method of induction of sepsis, and fluid administration had no effect on RBF. In contrast, on univariate analysis, state of consciousness of animals (P = 0.005), recovery after surgery (P < 0.001), haemodynamic pattern (hypodynamic or hyperdynamic state; P < 0.001) and cardiac output (P < 0.001) influenced RBF. However, multivariate analysis showed that only cardiac output remained an independent determinant of RBF (P < 0.001).

Conclusion

The impact of sepsis on RBF in humans is unknown. In experimental sepsis, RBF was reported to be decreased in two-thirds of studies (62 %) and unchanged or increased in one-third (38%). On univariate analysis, several factors not directly related to sepsis appear to influence RBF. However, multivariate analysis suggests that cardiac output has a dominant effect on RBF during sepsis, such that, in the presence of a decreased cardiac output, RBF is typically decreased, whereas in the presence of a preserved or increased cardiac output RBF is typically maintained or increased.     

Evaluating suspected sepsis in term neonates

BackgroundTerm newborns commonly undergo evaluations to ‘rule out sepsis’, although the frequency of this practice is unknown. Consequences may include increased duration of hospitalisation, admission to the neonatal unit and mother-infant separation, with interrupted breastfeeding.MethodNewborn infants delivered ≥ 37 weeks gestation without congenital anomalies that had blood cultures performed in January and February 2008 were audited. Sepsis-associated maternal, perinatal and neonatal parameters were collected to classify each infant as having definite, clinical, or no sepsis.Results54 of 944 term infants (5.7%) had blood cultures taken to rule out sepsis: 43 (80%) were negative, 11 (20%) had clinical sepsis and none had definite sepsis (3 had contaminants). The majority of evaluations were undertaken in the neonatal unit (59%) or the postnatal ward (34%), with respiratory distress the most frequent indication (38%). Infants with clinical sepsis were more likely to receive resuscitation at birth and to be admitted to the neonatal unit. Of all infants evaluated, 3 received antibiotics for longer than indicated, 1 had antibiotics discontinued early and one infant had antibiotics prescribed that were not optimal.Conclusions‘Rule out sepsis’ evaluations are common. Clinical guidelines together with ongoing education and vigilance regarding blood culture collection as well as choice and duration of antibiotics are important.     

Incidence and mortality of severe sepsis in surgical intensive care patients: the influence of patient gender on disease process and outcome

Objective: Laboratory studies demonstrated significant detrimental effects of male sex-steroids (testosterone) on immune functions following hemorrhagic shock and soft-tissue trauma. Moreover, better survival of female mice subjected to severe sepsis was observed when compared to male animals. The aims of the present study were to evaluate whether or not gender differences regarding incidence and mortality of severe sepsis do exist in surgical intensive care patients and to elucidate the influence of patient age on incidence and mortality of severe sepsis/septic shock.¶Design: Data base review of prospectively collected data from surgical intensive care patients.¶Setting: Surgical intensive care unit of the department of surgery of a university hospital.¶Patients: Prospectively collected data of 4218 intensive care patients (2709 male, 1509 female).¶Results: Significantly fewer female patients were referred to the intensive care unit (6.6 % vs 10.8 % of all patients; P < 0.05) leading to a significantly smaller proportion of female intensive care patients (35.8 % vs 64.2 %). No gender differences regarding number of failing organs or surgical procedure (exception vascular surgery) were observed in patients with and without severe sepsis/septic shock, indicating that the patients studied are comparable regarding general health prior to admission to SICU. Among all female patients referred to SICU only 7.6 % developed severe sepsis/septic shock, while 10.4 % of all male patients suffered from severe sepsis or septic shock (P < 0.05). This gender difference results from a significantly lower incidence of severe sepsis/septic shock in female patients between 60 and 79 years. No gender difference regarding mortality rates of severe sepsis/septic shock was observed (men 64.9 %, women 65.5 %).¶Conclusions: Our results indicate a significantly smaller number of female patients requiring intensive care as well as a significantly lower incidence of severe sepsis/septic shock in female intensive care patients. Mortality from severe sepsis/septic shock, however, is not affected by gender.     

Protease-activated receptor-1: key player in the sepsis coagulation-inflammation crosstalk

Protease-activated receptors (PARs) belong to the family of G protein-coupled receptors. Among the four members, PAR1 plays a major role in orchestrating the interactions between coagulation and inflammation. PAR1 has opposing functions during sepsis, and PAR1 blockade or activation may be alternatively beneficial at early or late stages of different sepsis models. Studying molecular mechanisms of the crosstalk between inflammation and coagulation may lead to the identification of new targets for therapies in sepsis. However, the time-dependent switch of PAR1 from an exacerbating proinflammatory receptor to a protective anti-inflammatory receptor needs to be investigated before clinical trials can be recommended. Finally, as PAR1 seems to play a singular role in Streptococcus pneumoniae-induced sepsis through a crosstalk between PAR1 and platelet-activating factor receptor, the exact role of PAR1 needs to be investigated in other models of sepsis.     

Procalcitonin for early diagnosis and differentiation of SIRS, sepsis, severe sepsis, and septic shock

Objective: To determine the value of procalcitonin (PCT) in the early diagnosis (and differentiation) of patients with SIRS, sepsis, severe sepsis, and septic shock in comparison to C-reactive protein (CRP), white blood cell and thrombocyte count, and APACHE-II score (AP-II).¶Design: Prospective cohort study including all consecutive patients admitted to the ICU with the suspected diagnosis of infection over a 7-month period.¶Patients and methods: A total of 185 patients were included: 17 patients with SIRS, 61 with sepsis, 68 with severe sepsis, and 39 patients with septic shock. CRP, cell counts, AP-II and PCT were evaluated on the first day after onset of inflammatory symptoms.¶Results: PCT values were highest in patients with septic shock (12.89 - 4.39 ng/ml; P < 0.05 vs patients with severe sepsis). Patients with severe sepsis had significantly higher PCT levels than patients with sepsis or SIRS (6.91 - 3.87 ng/ml vs 0.53 - 2.9 ng/ml; P < 0.001, and 0.41 - 3.04 ng/ml; P < 0.001, respectively). AP-II scores did not differ significantly between sepsis, severe sepsis and SIRS (19.26 - 1.62, 16.09 - 2.06, and 17.42 - 1.72 points, respectively), but was significantly higher in patients with septic shock (29.27 - 1.35, P < 0.001 vs patients with severe sepsis). Neither CRP, cell counts, nor the degree of fever showed significant differences between sepsis and severe sepsis, whereas white blood cell count and platelet count differed significantly between severe sepsis and septic shock.¶Conclusions: In contrast to AP-II, PCT appears to be a useful early marker to discriminate between sepsis and severe sepsis.     

Ketamine delays mortality in an experimental model of hemorrhagic shock and subsequent sepsis

BackgroundIn previous studies ketamine was reported to improve survival and decrease serum interleukin-6 (IL-6) concentration after sepsis alone and after burn injury followed by sepsis. The aim of this study was to determine whether ketamine alters survival and/or IL-6 after hemorrhagic shock alone or hemorrhagic shock followed by sepsis.Materials and methodsRats were subjected to hemorrhagic shock with or without subsequent Gram-negative bacterial sepsis and were either treated with ketamine 5 mg/kg or were not treated. Blood was sampled for IL-6 determination prior to hemorrhage, at the completion of resuscitation, and at 6 and 30 h later. Mortality was recorded for 7 days following hemorrhage or hemorrhage + sepsis.ResultsAfter hemorrhage + sepsis the time to median mortality was significantly later in the ketamine-treated group (36 h) than in the control group (12 h). At 12 h the survival rate of the ketamine-treated group (100%) was significantly higher than in the control group (55%). There were no significant differences between groups with respect to IL-6 or 7-day survival after either hemorrhage + sepsis or hemorrhage alone.ConclusionKetamine improved 12 h survival and delayed mortality after hemorrhage + sepsis without significantly altering IL-6, and did not alter survival or IL-6 after hemorrhage alone.