Biomarker Assessment of a High-Risk, Data-Driven Pediatric Sepsis Phenotype Characterized by Persistent Hypoxemia, Encephalopathy, and Shock.

OBJECTIVES: Identification of children with sepsis-associated multiple organ dysfunction syndrome (MODS) at risk for poor outcomes remains a challenge. We sought to the determine reproducibility of the data-driven "persistent hypoxemia, encephalopathy, and shock" (PHES) phenotype and determine its association with inflammatory and endothelial biomarkers, as well as biomarker-based pediatric risk strata. DESIGN: We retrained and validated a random forest classifier using organ dysfunction subscores in the 2012-2018 electronic health record (EHR) dataset used to derive the PHES phenotype. We used this classifier to assign phenotype membership in a test set consisting of prospectively (2003-2023) enrolled pediatric septic shock patients. We compared profiles of the PERSEVERE family of biomarkers among those with and without the PHES phenotype and determined the association with established biomarker-based mortality and MODS risk strata. SETTING: Twenty-five PICUs across the United States. PATIENTS: EHR data from 15,246 critically ill patients with sepsis-associated MODS split into derivation and validation sets and 1,270 pediatric septic shock patients in the test set of whom 615 had complete biomarker data. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The area under the receiver operator characteristic curve of the modified classifier to predict PHES phenotype membership was 0.91 (95% CI, 0.90-0.92) in the EHR validation set. In the test set, PHES phenotype membership was associated with both increased adjusted odds of complicated course (adjusted odds ratio [aOR] 4.1; 95% CI, 3.2-5.4) and 28-day mortality (aOR of 4.8; 95% CI, 3.11-7.25) after controlling for age, severity of illness, and immunocompromised status. Patients belonging to the PHES phenotype were characterized by greater degree of systemic inflammation and endothelial activation, and were more likely to be stratified as high risk based on PERSEVERE biomarkers predictive of death and persistent MODS. CONCLUSIONS: The PHES trajectory-based phenotype is reproducible, independently associated with poor clinical outcomes, and overlapped with higher risk strata based on prospectively validated biomarker approaches.

Quantitative Assessment of Blood Lactate in Shock: Measure of Hypoxia or Beneficial Energy Source.

Blood lactate concentration predicts mortality in critically ill patients and is clinically used in the diagnosis, grading of severity, and monitoring response to therapy of septic shock. This paper summarizes available quantitative data to provide the first comprehensive description and critique of the accepted concepts of the physiology of lactate in health and shock, with particular emphasis on the controversy of whether lactate release is simply a manifestation of tissue hypoxia versus a purposeful transfer ("shuttle") of lactate between tissues. Basic issues discussed include (1) effect of nonproductive lactate-pyruvate exchange that artifactually enhances flux measurements obtained with labeled lactate, (2) heterogeneous tissue oxygen partial pressure (Krogh model) and potential for unrecognized hypoxia that exists in all tissues, and (3) pathophysiology that distinguishes septic from other forms of shock. Our analysis suggests that due to exchange artifacts, the turnover rate of lactate and the lactate clearance are only about 60% of the values of 1.05 mmol/min/70 kg and 1.5 L/min/70 kg, respectively, determined from the standard tracer kinetics. Lactate turnover reflects lactate release primarily from muscle, gut, adipose, and erythrocytes and uptake by the liver and kidney, primarily for the purpose of energy production (TCA cycle) while the remainder is used for gluconeogenesis (Cori cycle). The well-studied physiology of exercise-induced hyperlactatemia demonstrates massive release from the contracting muscle accompanied by an increased lactate clearance that may occur in recovering nonexercising muscle as well as the liver. The very limited data on lactate kinetics in shock patients suggests that hyperlactatemia reflects both decreased clearance and increased production, possibly primarily in the gut. Our analysis of available data in health and shock suggests that the conventional concept of tissue hypoxia can account for most blood lactate findings and there is no need to implicate a purposeful production of lactate for export to other organs.

Assessment of early renal angina index for prediction of subsequent severe acute kidney injury during septic shock in children.

BACKGROUND: Acute kidney injury (AKI) is independently related to the adverse outcome of septic shock, but it lacks effective early predictors. Renal anginal index (RAI) was used to predict subsequent severe AKI (AKIs) in critically ill patients. The application of RAI in children with septic shock has not been reported. This study aims to evaluate the efficacy of early RAI in predicting subsequent AKIs within 3 days after PICU admission in children with septic shock by comparing with early fluid overload (FO) and early creatinine elevation. METHODS: Sixty-six children admitted to PICU aged 1 month to 16 years old, with septic shock from January 2016 to December 2019 were analyzed retrospectively. According to the 2012 Kidney Disease Improving Global outcomes (KDIGO) criteria, AKIs was defined by the KDIGO stage ≥2 within 3 days after PICU admission. Early RAI positive (RAI+) was defined as RAI ≥ 8 within 12 h of PICU admission. Any elevation of serum creatinine (SCr) over baseline within 12 h after PICU admission was denoted as "Early SCr > base". Early FO positive (FO+) was defined as FO > 10% within 24 h of PICU admission. RESULTS: Of 66 eligible cases, the ratio of early RAI+, early SCr > base, early FO+ was 57.57, 59.09 and 16.67% respectively. The incidence of AKIs in early RAI+ group (78.94%) was higher than that in early RAI- group (21.42%) (p = 0.04), and there was no significant difference compared with the early FO+ group (71.79%) and early SCr > base group (81.82%) (P > 0.05). After adjustment for confounders, early RAI+ was independently associated with the occurrence of AKIs within 3 days (OR 10.04, 95%CI 2.39-42.21, p < 0.01). The value of early RAI+ (AUC = 0.78) to identify patients at high risk of AKIs was superior to that of early SCr > base (AUC = 0.70) and early FO+ (AUC = 0.58). A combination of serum lactate with early RAI+ improved the predictive performance for assessing AKIs (AUC = 0.83). CONCLUSIONS: Early RAI could be used as a more convenient and effective index to predict the risk of AKIs in children with septic shock within 3 days. Early RAI+ combined with serum lactate improved the predictive performance for assessing AKIs.

Rapid Diagnostics for Blood Cultures: Supporting Decisions for Antimicrobial Therapy and Value-Based Care.

Bacteremia and sepsis are critically important syndromes with high mortality, morbidity, and associated costs. Bloodstream infections and sepsis are among the top causes of mortality in the US, with >600 deaths each day. Most septic patients can be found in emergency medicine departments or critical care units, settings in which rapid administration of targeted antibiotic therapy can reduce mortality. Unfortunately, routine blood cultures are not rapid enough to aid in the decision of therapeutic intervention at the onset of bacteremia. As a result, empiric, broad-spectrum treatment is common-a costly approach that may fail to target the correct microbe effectively, may inadvertently harm patients via antimicrobial toxicity, and may contribute to the evolution of drug-resistant microbes. To overcome these challenges, laboratorians must understand the complexity of diagnosing and treating septic patients, focus on creating algorithms that rapidly support decisions for targeted antibiotic therapy, and synergize with existing emergency department and critical care clinical practices put forth in the Surviving Sepsis Guidelines.

Utility of admission lactate concentration, lactate variables, and shock index in outcome assessment in dogs diagnosed with shock.

OBJECTIVE: To determine whether admission venous plasma lactate concentration, calculated lactate variables, or shock index (SI) could discriminate hospital survivors from nonsurvivors in dogs admitted with shock. DESIGN: Prospective investigation performed over a 19-month period. SETTING: Large urban private teaching hospital. ANIMALS: Twenty-three dogs consecutively admitted to the ICU from January 2008 to July 2009 with initial peripheral venous plasma lactate concentration >2 mmol/L (18.0 mg/dL) and clinical and hemodynamic parameters consistent with shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Heart rate, systolic blood pressure, and venous plasma lactate concentrations were serially recorded at predefined time points and used to calculate SI (SI = heart rate/systolic blood pressure) and lactate variables, including lactime (time lactate > 2.0 mmol/L), lactate clearance ([lactateinitial - lactatedelayed ]/lactateinitial × 100), and LACAREA (area under the lactate concentration versus time curve). Primary outcome was survival to discharge. Overall survival rate was 61%. Admission venous plasma lactate concentration did not differ between groups (P = 0.2). Lactime was shorter in survivors versus nonsurvivors (P = 0.02). Lactate clearance at 1, 10, 16, 24, and 36 hours, and final lactate clearance were greater in survivors versus nonsurvivors (P < 0.05). LACAREA at time intervals 0-1, 1-4, 4-10, 10-16, 16-24, 24-30, and 30-36 hours was larger in nonsurvivors versus survivors (P < 0.05). Total LACAREA did not differ between groups (P = 0.09). Admission SI and time to normalize SI (SI < 0.9) were not different between survivors and nonsurvivors (P > 0.05). CONCLUSIONS: While admission venous plasma lactate concentration could not discriminate between hospital survivors and nonsurvivors, lactate variables showed clinical utility to predict outcome in dogs with shock. Further studies are needed to determine SI reference ranges and optimal SI cut-off values to improve its prognostic ability in sick dogs.

Pre-operative labs: Wasted dollars or predictors of post-operative cardiac and septic events in orthopaedic trauma patients?

PURPOSE: As US healthcare expenditures continue to rise, there is significant pressure to reduce the cost of inpatient medical services. Studies have estimated that over 70% of routine labs may not yield clinical benefits while adding over $300 in costs per day for every inpatient. Although orthopaedic trauma patients tend to have longer inpatient stays and hip fractures have been associated with significant morbidity, there is a dearth of data examining pre-operative labs in predicting post-operative adverse events in these populations. The purpose of this study was to assess whether pre-operative labs significantly predict post-operative cardiac and septic complications in orthopaedic trauma and hip fracture patients. METHODS: Between 2006 and 2013, 56,336 (15.6%) orthopaedic trauma patients were identified and 27,441 patients (7.6%) were diagnosed with hip fractures. Pre-operative labs included sodium, BUN, creatinine, albumin, bilirubin, SGOT, alkaline phosphatase, white count, hematocrit, platelet count, prothrombin time, INR, and partial thromboplastin time. For each of these labs, patients were deemed to have normal or abnormal values. Patients were noted to have developed cardiac or septic complications if they sustained (1) myocardial infarction (MI), (2) cardiac arrest, or (3) septic shock within 30 days after surgery. Separate regressions incorporating over 40 patient characteristics including age, gender, pre-operative comorbidities, and labs were performed for orthopaedic trauma patients in order to determine whether pre-operative labs predicted adverse cardiac or septic outcomes. RESULTS: 749 (1.3%) orthopaedic trauma patients developed cardiac complications and 311 (0.6%) developed septic shock. Multivariate regression demonstrated that abnormal pre-operative platelet values were significantly predictive of post-operative cardiac arrest (OR: 11.107, p=0.036), and abnormal bilirubin levels were predictive (OR: 8.487, p=0.008) of the development of septic shock in trauma patients. In the hip fracture cohort, abnormal partial thromboplastin time was significantly associated with post-operative myocardial infarction (OR: 15.083, p=0.046), and abnormal bilirubin (OR: 58.674, p=0.002) significantly predicted the onset of septic shock. CONCLUSIONS: This is the first study to demonstrate the utility of pre-operative labs in predicting perioperative cardiac and septic adverse events in orthopaedic trauma and hip fracture patients. Particular attention should be paid to haematologic/coagulation labs (platelets, PTT) and bilirubin values. LEVEL OF EVIDENCE: Prognostic Level II.

Emergency Department Management of Sepsis Patients: A Randomized, Goal-Oriented, Noninvasive Sepsis Trial.

STUDY OBJECTIVE: The noninvasive cardiac output monitor and passive leg-raising maneuver has been shown to be reasonably accurate in predicting fluid responsiveness in critically ill patients. We examine whether using a noninvasive protocol would result in more rapid lactate clearance after 3 hours in patients with severe sepsis and septic shock in the emergency department. METHODS: In this open-label randomized controlled trial, 122 adult patients with sepsis and serum lactate concentration of greater than or equal to 3.0 mmol/L were randomized to receive usual care or intravenous fluid bolus administration guided by measurements of change of stroke volume index, using the noninvasive cardiac output monitor after passive leg-raising maneuver. The primary outcome was lactate clearance of more than 20% at 3 hours. Secondary outcomes included mortality, length of hospital and ICU stay, and total hospital cost. Analysis was intention to treat. RESULTS: Similar proportions of patients in the randomized intervention group (70.5%; N=61) versus control group (73.8%; N=61) achieved the primary outcome, with a relative risk of 0.96 (95% confidence interval [CI] 0.77 to 1.19). Secondary outcomes were similar in both groups (P>.05 for all comparisons). Hospital mortality occurred in 6 patients (9.8%) each in the intervention and control groups on or before 28 days (relative risk=1.00; 95% CI 0.34 to 2.93). Among a subgroup of patients with underlying fluid overload states, those in the intervention group tended to receive clinically significantly more intravenous fluids at 3 hours (difference=975 mL; 95% CI -450 to 1,725 mL) and attained better lactate clearance (difference=19.7%; 95% CI -34.6% to 60.2%) compared with the control group, with shorter hospital lengths of stay (difference=-4.5 days; 95% CI -9.5 to 2.5 days). CONCLUSION: Protocol-based fluid resuscitation of patients with severe sepsis and septic shock with the noninvasive cardiac output monitor and passive leg-raising maneuver did not result in better outcomes compared with usual care. Future studies to demonstrate the use of the noninvasive protocol-based care in patients with preexisting fluid overload states may be warranted.

Population pharmacokinetics of piperacillin in the early phase of septic shock: does standard dosing result in therapeutic plasma concentrations?

Antibiotic dosing in septic shock patients poses a challenge for clinicians due to the pharmacokinetic (PK) variability seen in this patient population. Piperacillin-tazobactam is often used for empirical treatment, and initial appropriate dosing is crucial for reducing mortality. Accordingly, we determined the pharmacokinetic profile of piperacillin (4 g) every 8 h, during the third consecutive dosing interval, in 15 patients treated empirically for septic shock. We developed a population pharmacokinetic model to assess empirical dosing and to simulate alternative dosing regimens and modes of administration. Time above the MIC (T>MIC) predicted for each patient was evaluated against clinical breakpoint MIC for Pseudomonas aeruginosa (16 mg/liter). Pharmacokinetic-pharmacodynamic (PK/PD) targets evaluated were 50% fT>4×MIC and 100% fT>MIC. A population PK model was developed using NONMEM, and data were best described by a two-compartment model. Central and intercompartmental clearances were 3.6 liters/h (relative standard error [RSE], 15.7%) and 6.58 liters/h (RSE, 16.4%), respectively, and central and peripheral volumes were 7.3 liters (RSE, 11.8%) and 3.9 liters (RSE, 9.7%), respectively. Piperacillin plasma concentrations varied considerably between patients and were associated with levels of plasma creatinine. Patients with impaired renal function were more likely to achieve predefined PK/PD targets than were patients with preserved or augmented renal function. Simulations of alternative dosing regimens showed that frequent intermittent bolus dosing as well as dosing by extended and continuous infusion increases the probability of attaining therapeutic plasma concentrations. For septic shock patients with preserved or augmented renal function, dose increment or prolonged infusion of the drug needs to be considered. (This study has been registered at ClinicalTrials.gov under registration no. NCT02306928.).

A combination of early warning score and lactate to predict intensive care unit transfer of inpatients with severe sepsis/septic shock.

BACKGROUND/AIMS: The modified early warning score (MEWS) is used to predict patient intensive care unit (ICU) admission and mortality. Lactate (LA) in the blood lactate (BLA) is measured to evaluate disease severity and treatment efficacy in patients with severe sepsis/septic shock. The usefulness of a combination of MEWS and BLA to predict ICU transfer in severe sepsis/septic shock patients is unclear. We evaluated whether use of a combination of MEWS and BLA enhances prediction of ICU transfer and mortality in hospitalized patients with severe sepsis/septic shock. METHODS: Patients with severe sepsis/septic shock who were screened or contacted by a medical emergency team between January 2012 and August 2012 were enrolled at a university-affiliated hospital with ~2,700 beds, including 28 medical ICU beds. RESULTS: One hundred patients were enrolled and the rate of ICU admittance was 38%. MEWS (7.37 vs. 4.85) and BLA concentration (5 mmol/L vs. 2.19 mmol/L) were significantly higher in patients transferred to ICU than those in patients treated in general wards. The combination of MEWS and BLA was more accurate than MEWS alone in terms of ICU transfer (C-statistics: 0.898 vs. 0.816, p = 0.019). The 28-day mortality rate was 19%. MEWS was the only factor significantly associated with 28-day mortality rate (odds ratio, 1.462; 95% confidence interval, 1.122 to 1.905; p = 0.005). CONCLUSIONS: The combination of MEWS and BLA may enhance prediction of ICU transfer in patients with severe sepsis/septic shock.

Customized Internal Reference Controls for Improved Assessment of Circulating MicroRNAs in Disease.

BACKGROUND: Altered levels of circulating extracellular miRNA in plasma and serum have shown promise as non-invasive biomarkers of disease. However, unlike the assessment of cellular miRNA levels for which there are accepted housekeeping genes, analogous reference controls for normalization of circulating miRNA are lacking. Here, we provide an approach to identify and validate circulating miRNA reference controls on a de novo basis, and demonstrate the advantages of these customized internal controls in different disease settings. Importantly, these internal controls overcome key limitations of external spike-in controls. METHODS: Using a global RT-qPCR screen of 1066 miRNAs in plasma from pulmonary hypertension patients (PAH) and healthy subjects as a case example, we identified a large pool of initial candidate miRNAs that were systematically ranked according to their plasma level stability using a predefined algorithm. The performance of the top candidates was validated against multiple comparators, and in a second independent cohort of PAH and control subjects. The broader utility of this approach was demonstrated in a completely different disease setting with 372 miRNAs screened in plasma from septic shock patients and healthy controls. RESULTS: Normalization of data with specific internal reference controls significantly reduced the overall variation in circulating miRNA levels between subjects (relative to raw data), provided a more balanced distribution of up- and down-regulated miRNAs, replicated the results obtained by the benchmark geometric averaging of all detected miRNAs, and outperformed the commonly used external spike-in strategy. CONCLUSIONS: We demonstrate the feasibility of identifying circulating reference controls that can reduce extraneous technical variations, and improve the assessment of disease-related changes in plasma miRNA levels. This study provides a novel conceptual framework that addresses a critical and previously unmet need if circulating miRNAs are to advance as reliable diagnostic tools in medicine.

Prognostic value of B-type natriuretic peptide with the sequential organ failure assessment score in septic shock.

BACKGROUND: The aim of this study was to evaluate the prognostic value of B-type natriuretic peptide (BNP) in combination with the sequential organ failure assessment (SOFA) score in patients with septic shock at the time of emergency department (ED). METHODS: Study subjects included all consecutive patients with septic shock who were treated with resuscitation bundle therapy between January 2010 and July 2012. SOFA scores and BNP were measured at ED recognition. The primary outcome was 28-day mortality. The area under the receiver operating characteristic curve was used to compare the predictive ability of SOFA score alone and in combination with BNP. RESULTS: A total of 290 patients with septic shock admitted to ED were included. The BNP and SOFA score were higher in nonsurvival group compared with survival group (1,156.0 versus 469.1 pg/mL, P < 0.01; 9.9 versus 8.0, P < 0.01). In the receiver operating characteristic curves for predicting 28-day mortality, the area under the curves of SOFA score combined with BNP was 0.728 (95% confidence interval [CI]: 0.658-0.798) and SOFA score alone was 0.682 (95% CI: 0.610-0.755). Although the predictive ability of SOFA with BNP was statistically higher than that of SOFA alone (P = 0.02), it could not increase prognostic accuracy clinically significantly. SOFA with BNP was an independent predictor of 28-day mortality (odds ratio: 1.40, 95% CI: 1.15-1.71). CONCLUSIONS: The combination of SOFA with BNP at the time of ED presentation may provide superior prognostic accuracy to the patients with septic shock. However, further studies need to validate the prognostic usefulness of SOFA with BNP.

Pharmacokinetics of doripenem during high volume hemodiafiltration in patients with septic shock.

Pharmacokinetics (PK) of doripenem was determined during high volume hemodiafiltration (HVHDF) in patients with septic shock. A single 500 mg dose of doripenem was administered as a 1 hour infusion during HVHDF to 9 patients. Arterial blood samples were collected before and at 30 or 60 minute intervals over 8 hours (12 samples) after study drug administration. Doripenem concentrations were determined by ultrahigh performance liquid chromatography-tandem mass spectrometry. Population PK analysis and Monte Carlo simulation of 1,000 subjects were performed. The median convective volume of HVHDF was 10.3 L/h and urine output during the sampling period was 70 mL. The population mean total doripenem clearance on HVHDF was 6.82 L/h, volume of distribution of central compartment 10.8 L, and of peripheral compartment 12.1 L. Doses of 500 mg every 8 hours resulted in 88.5% probability of attaining the target of 50% time over MIC for bacteria with MIC = 2 µg/mL at 48 hours, when doubling of MIC during that time was assumed. Significant elimination of doripenem occurs during HVHDF. Doses of 500 mg every 8 hours are necessary for treatment of infections caused by susceptible bacteria during extended HVHDF.

[The role of end-tidal carbon dioxide partial pressure in fluid responsiveness assessment in septic shock patient].

OBJECTIVE: To assess whether end-tidal carbon dioxide partial pressure (PETCO2) can predict the fluid responsiveness in septic shock patients. METHODS: Septic shock patients under mechanical ventilation without spontaneous breathing and with the need of a fluid challenge test were included in this study.Heart rate, central venous pressure, pulse pressure, PETCO2, and CI before and after the fluid challenge test were conducted in all the patients. RESULTS: Of the 48 septic shock patients included, 34 had preload responsiveness, 14 had no responsiveness. ΔCI and ΔPETCO2 after the fluid challenge test in "volume responders" were (0.85 ± 0.47) L×min(-1)×m(-2) and (3.5 ± 2.5) mmHg respectively, which were higher than those in "no volume responders"(P < 0.05). The fluid-induced changes in PETCO2 and CI were correlated (r = 0.072, P < 0.05). The AUCROC of fluid challenge-induced ΔPETCO2 as the predictor for volume responsiveness was 0.943, and its sensitivity was 87.9% and specificity was 93.4% with a critical value of 5%. The AUCROC of ΔPP as the predictor for volume responsiveness was 0.801, and its sensitivity was 68.1% and specificity was 73.2% with a critical value of 10%. CONCLUSION: The changes of PETCO2 induced by a fluid challenge test can predict fluid responsiveness with reliability, and have a better sensitivity and specificity than the changes of PP.

Impact of prothrombin time-International Normalized Ratio on outcome of patients with septic shock receiving polymyxin B cartridge hemoperfusion.

BACKGROUND: Although most patients with septic shock have a poor outcome, some may survive after blood purification treatment such as polymyxin B cartridge hemoperfusion (PMX). OBJECTIVE: To explore the most significant characteristic associated with 28-day mortality in patients with septic shock receiving PMX. METHODS: Between April 2006 and March 2008, 116 patients with septic shock who had received PMX in a prospectively collected multicenter collaborative study were enrolled. Uni- and multivariate analyses using the Cox proportional hazard model were performed to assess the most significant clinical characteristic that was associated with 28-day mortality. RESULTS: Among 33 clinicolaboratory characteristics, receiver operating characteristic (ROC) curve analyses selected 12 characteristics with recommended cutoff values such as HCO(3)(-) (≤19.8/>19.8; mEq/L), base excess (≤-5.35/>-5.35; mEq/L), diastolic blood pressure (≤48/>48 mmHg), mean arterial pressure (≤73/>73 mmHg), pH (≤7.29/>7.29), interleukin-6 (≤19,150/>19,150 pg/dL), prothrombin time-International Normalized Ratio (PT-INR; ≤2.05/>2.05), predictive value of Acute Physiology and Chronic Health Evaluation II (APACHE II; ≤0.4/>0.4), pyruvate (≤1.82/>1.82 mg/dL), APACHE II score (≤21/>21), acetate/pyruvate ratio (≤19/>19), and acetate (≤44.8/>44.8 mg/dL) on the basis of large area under the ROC curves for 28-day mortality. The results of uni- and multivariate analyses using these selected characteristics revealed that only PT-INR (≤2.05/>2.05; hazard ratio, 2.823; 95% CI, 1.243-6.412; P = .013) was associated with 28-day mortality. Survival curve analysis demonstrated a significant difference in 28-day mortality between patients with lower (≤2.05) and higher (>2.05) PT-INR (P < .001). CONCLUSION: Prolonged PT-INR is an independent risk factor for 28-day mortality in patients receiving PMX for septic shock.

Clinical and economic impact of procalcitonin to shorten antimicrobial therapy in septic patients with proven bacterial infection in an intensive care setting.

Biomarkers such as procalcitonin (PCT) have been studied to guide duration of antibiotic therapy. We aimed to assess whether a decrease in PCT levels could be used to reduce the duration of antibiotic therapy in intensive care unit (ICU) patients with a proven infection without risking a worse outcome. We assessed 265 patients with suspected sepsis, severe sepsis, or septic shock in our ICU. Of those, we randomized 81 patients with a proven bacterial infection into 2 groups: an intervention group in which the duration of the antibiotic therapy was guided by a PCT protocol and a control group in which there was no PCT guidance. In the per-protocol analysis, the median antibiotic duration was 9 days in the PCT group (n = 20) versus 13 days in the non-PCT group (n = 31), P = 0.008. This study demonstrates that PCT can be a useful tool for limiting antimicrobial therapy in ICU patients with documented bacterial infection.

[Integral assessment of endogenous intoxication in patients with phlegmons of maxillofacial area].

The study assessed the correlation of red blood cells structural and functional disorders as a result of tissue metabolism changes and accumulation of final and intermediate metabolic products in association with microbial toxins, as well as changes of plasma general antioxidation capacities with clinical manifestations and degree of endogenous intoxication syndrome in patients with widespread phlegmons of maxillofacial area. The red blood cell structure served as an indicator of all biological membranes condition. The correction of red blood cells structure was achieved by administration of membranoprotective antioxidants.

[Value of peripheral perfusion index in the assessment of reactive hyperemia in septic patients].

OBJECTIVE: To explore the changes of peripheral perfusion index (PI) during forearm vascular occlusion test (VOT) and examine its evaluative value of reactive hyperemia in septic patients. METHODS: Twenty-one patients with septic shock, 21 postoperative ones without infection and 18 health volunteers were prospectively recruited to undergo vascular occlusion test. An arrest of forearm blood flow was applied for 3 min with a sphygmomanometer inflated to a pressure approximately 30 mm Hg greater than systolic pressure around forearm. PI was measured and recorded continuously by conventional pulse oximetry during VOT. RESULTS: (1)In all subjects, the PI values decreased to zero during ischemic period. There were no changes in heart rate or blood pressure between baseline and reperfusion. The maximum PI (PI-max) after a release of pneumatic cuff was significantly higher than baseline PI; (2)The change rates of PI-max and PI were significantly lower and the time to PI-max was longer in septic group after reperfusion; (3) A negative relationship existed between PI change rate and sequential organ failure assessment (SOFA) score in septic group. CONCLUSIONS: PI may be used to assess vascular reactive hyperemia in critically ill patients. And the capacity of peripheral vascular reactive hyperemia decreases in septic patients.

Development of an immunoassay for the derived-peptide of chromogranin A, vasostatin-I (1-76): assessment of severity in patients with sepsis.

CONTEXT: Proteolytic fragments of chromogranin A (CgA) including the CgA 1-76 fragment (called vasostatin-I [VS-I]) could be a useful biomarker of sepsis, but there is no available immunoassay. METHODS: A sandwich ELISA for VS-I was developed, and plasma VS-I was measured in 30 healthy controls and 60 critically ill patients with sepsis. RESULTS: The ELISA showed intra- and inter-assay coefficients of variations (CVs) below 4 and 9%. Plasma VS-I was significantly increased compared with controls in patients with sepsis, severe sepsis, and sepsis shock (p < 0.0001). Receiver operating curve (ROC) analyses indicated that plasma VS-I was more sensitive and specific than plasma CgA to diagnose sepsis and to assess its severity. CONCLUSIONS: The measurements of plasma VS-I with this new ELISA may be useful for the clinical investigation of patients with sepsis.