calca-protein--human and Multiple-Organ-Failure

Persistent organ failure and infected pancreatic necrosis are major determinants of mortality in acute pancreatitis, but there is a gap in the literature assessing the best available predictors of these two determinants. The purpose of this review was to investigate the utility of predictors of persistent organ failure and infected pancreatic necrosis in patients with acute pancreatitis, both alone and in combination.. We performed a systematic search of the literature in 3 databases for prospective studies evaluating predictors of persistent organ failure, infected pancreatic necrosis, or both, with strict eligibility criteria.. The best predictors of persistent organ failure were the Japanese Severity Score and Bedside Index of Severity in Acute Pancreatitis when the evaluation was performed within 48h of admission, and blood urea nitrogen and Japanese Severity Score after 48h of admission. Systemic Inflammation Response Syndrome was a poor predictor of persistent organ failure. The best predictor of infected pancreatic necrosis was procalcitonin.. Based on the best available data, it is justifiable to use blood urea nitrogen for prediction of persistent organ failure after 48h of admission and procalcitonin for prediction of infected pancreatic necrosis in patients with confirmed pancreatic necrosis. There is no predictor of persistent organ failure that can be justifiably used in clinical practice within 48h of admission.

Topics: Acute Disease; Blood Urea Nitrogen; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Disease Progression; Humans; Multiple Organ Failure; Necrosis; Pancreas; Pancreatitis, Acute Necrotizing; Predictive Value of Tests; Protein Precursors; Severity of Illness Index; Systemic Inflammatory Response Syndrome

Severity stratification is a critical issue in acute pancreatitis that strongly influences diagnostic and therapeutic decision making. According to the widely used Atlanta classification, "severe" disease comprises various local and systemic complications that are associated with an increased risk of mortality. However, results from recent clinical studies indicate that these complications vary in their effect on outcome, and many are not necessarily life threatening on their own. Therefore, "severe," as defined by Atlanta, must be distinguished from "prognostic," aiming at nonsurvival. In the first week after disease onset, pancreatitis-related organ failure is the preferred variable for predicting severity and prognosis because it outweighs morphologic complications. Contrast-enhanced CT and MRI allow for accurate stratification of local severity beyond the first week after symptom onset. Among the biochemical markers, C-reactive protein is still the parameter of choice to assess attack severity, although prognostic estimation is not possible. Other markers, including pancreatic protease activation peptides, interleukins-6 and -8, and polymorphonuclear elastase are useful early indicators of severity. Procalcitonin is one of the most promising single markers for assessment of major complications and prognosis throughout the disease course.

Topics: APACHE; Blood Coagulation Disorders; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Humans; Leukocyte Elastase; Multiple Organ Failure; Pancreatitis; Peptides; Protein Precursors; Serum Amyloid A Protein; Severity of Illness Index

Procalcitonin (PCT) is a protein consisting of 116 aminoacids with molecular weight 13 kDa. It is encoded by CALC-1 gene. According to the basic and clinical research results PCT appears to be a highly sensitive and specific marker reflecting severity of the systemic inflammatory response to infectious stimuli. Despite the investigation focused on CALC-1 gene, little is known about the biology of PCT and cellular sources of PCT during inflammation. One of the possible sources may be human peripheral blood mononuclear cells. PCT is an indicator of bacterial infections minimally stimulated by viral infections, autoimmune diseases and tumors.

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Infections; Multiple Organ Failure; Protein Precursors; Systemic Inflammatory Response Syndrome

Parenterally administered ascorbic acid modulates sepsis-induced inflammation and coagulation in experimental animal models. The objective of this randomized, double-blind, placebo-controlled, phase I trial was to determine the safety of intravenously infused ascorbic acid in patients with severe sepsis.. Twenty-four patients with severe sepsis in the medical intensive care unit were randomized 1:1:1 to receive intravenous infusions every six hours for four days of ascorbic acid: Lo-AscA (50 mg/kg/24 h, n = 8), or Hi-AscA (200 mg/kg/24 h, n = 8), or Placebo (5% dextrose/water, n = 8). The primary end points were ascorbic acid safety and tolerability, assessed as treatment-related adverse-event frequency and severity. Patients were monitored for worsened arterial hypotension, tachycardia, hypernatremia, and nausea or vomiting. In addition Sequential Organ Failure Assessment (SOFA) scores and plasma levels of ascorbic acid, C-reactive protein, procalcitonin, and thrombomodulin were monitored.. Mean plasma ascorbic acid levels at entry for the entire cohort were 17.9 ± 2.4 μM (normal range 50-70 μM). Ascorbic acid infusion rapidly and significantly increased plasma ascorbic acid levels. No adverse safety events were observed in ascorbic acid-infused patients. Patients receiving ascorbic acid exhibited prompt reductions in SOFA scores while placebo patients exhibited no such reduction. Ascorbic acid significantly reduced the proinflammatory biomarkers C-reactive protein and procalcitonin. Unlike placebo patients, thrombomodulin in ascorbic acid infused patients exhibited no significant rise, suggesting attenuation of vascular endothelial injury.. Intravenous ascorbic acid infusion was safe and well tolerated in this study and may positively impact the extent of multiple organ failure and biomarkers of inflammation and endothelial injury.. ClinicalTrials.gov identifier NCT01434121.

Topics: Adult; Aged; Aged, 80 and over; Ascorbic Acid; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Demography; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Multiple Organ Failure; Placebos; Protein Precursors; Sepsis; Thrombomodulin

Systemic inflammatory response syndrome (SIRS) and sepsis remain the leading cause of death in the critically ill. A reduction in the antioxidant capacity, including selenoenzymes that are dependent on selenium (Se), could be a contributing factor. Se supplementation in septic patients have yielded conflicting results. We hypothesized that a high-dose Se supplementation would (1) improve markers of inflammation, nutrition and antioxidant defence, and (2) decrease mortality.. This prospective, randomized, open-label, single-centre clinical trial included 150 patients with SIRS/sepsis and a SOFA score of >5. Patients in the Se+ group (n = 75) received Se for 14 days (1,000 μg on day 1,500 μg/day on days 2-14). Patients in both the control (Se-) group (n = 75) and the Se+ group received a standard Se dose (<75 μg/day). Plasma Se, whole-blood glutathione peroxidase (GPx) activity, C-reactive protein (CRP), procalcitonin (PCT), albumin, prealbumin and cholesterol levels, along with APACHE II and SOFA scores, were determined at baseline and on days 1-7 and day 14. Mortality was assessed at day 28.. Plasma Se and GPx activity were increased in the Se+ group from day 1 onwards. Negative correlations were demonstrated between plasma Se, CRP (P = 0.035), PCT (P = 0.022) and SOFA (P = 0.001) at admission but not on days 7 or 14. Prealbumin and cholesterol increased in the Se+ group versus the respective baselines. Mortality was similar between groups, with no gender differences.. High-dose Se substitution in patients with SIRS/sepsis increased plasma Se and GPx levels, but did not reduce mortality. Markers of inflammation were reduced similarly in both groups.

Topics: Adult; Aged; Antioxidants; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Female; Glutathione Peroxidase; Humans; Male; Middle Aged; Multiple Organ Failure; Prealbumin; Prospective Studies; Protein Precursors; Selenium; Sepsis

In surgical sepsis, the rapid identification of source of infection at an early stage after surgery or serious trauma is crucial for favorable outcome. The discrimination between local and generalized infection is critical for correct treatment.. In a randomized, controlled, single-centre study we investigated 72 patients with severe sepsis after major abdominal surgery or surgery for multiple trauma. Patients were divided in 2 groups: in the first group (PCT, n=38), more important role in the treatment decision was given to PCT level (severe sepsis with PCT >2 ng/mL signalled bacteremia and pushed us to change antibiotics and intravascular devices, severe sepsis with PCT < or =2 ng/mL prompted use of ultrasonography and/or CT, followed by repeated surgery in patients with localized infection). The control group (CON, n=34) was treated by standard evaluation of all parameters by consultant surgeon. We investigated 28-day all-cause mortality, sepsis-related complications, the duration of stay in the intensive care unit, and ventilated days.. The hospital mortality was in PCT group 26% and 38% in control group (p = 0.28). Average SOFA score was 7.9 +/- 2.8 in PCT group vs. 9.3 +/- 3.3 (p = 0.06). The decline of ICU days (16.1 +/- 6.9 vs. 19.4 +/- 8.9; p = 0.09) and ventilated days (10.3 +/- 7.8 vs. 13.9 +/- 9.4; p = 0.08) in PCT group was observed, but the difference was not significant.. We observed a clear tendency to decrease extent of multiple organ dysfunction syndrome in patients, in which therapeutic decision was made earlier using procalcitonin as an additional marker separating local infection from generalized one.

Topics: Abdomen; Adult; Aged; Aged, 80 and over; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cross Infection; Decision Support Techniques; Female; Humans; Injury Severity Score; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Postoperative Complications; Predictive Value of Tests; Protein Precursors; Reoperation; Respiration, Artificial; Sepsis

Our objective was to investigate whether short-term infusion of the oxygen free radical scavenger N-acetylcysteine (NAC) administered before and during extensive abdominal surgery could ameliorate the progression of early systemic inflammatory response.. Prospective, randomised, double-blinded, placebo-controlled clinical trial.. Twenty-bed intensive care unit in a university hospital.. Following written informed consent, 100 patients were randomised into NAC and placebo groups. Three patients from the NAC group and four from the placebo group withdrew before the final analysis.. The treatment group (n=47) received NAC (150 mg/kg(-1) bolus followed by a continuous infusion of 12 mg/kg(-1)/h(-1)) and the placebo group ( n=46) received the same volume of 5% dextrose during surgery.. Serum procalcitonin (PCT), C-reactive protein (CRP) and microalbuminuria was monitored preoperatively, on admission to ICU, then daily during the first 3 postoperative days. For statistical analysis Mann Whitney and Chi-squared tests were used. Patients' clinical course was similar in each group as monitored by the Multiple Organ Dysfunction Scores. There was no significant difference between the two groups regarding PCT and microalbuminuria at any assessment point. Significantly lower CRP levels were found in the NAC group on days 1 and 2 (t(24): median: 84.5 interquartile range: [62-120] vs. 118 [86-137] mg/l; p=0.020; t(48): 136 [103-232] vs. 195 [154-252] mg/l; p=0.013, NAC vs. placebo respectively).. In this study, short-term NAC treatment decreased CRP levels, but failed to attenuate any other inflammatory response, as monitored by serum PCT and microalbuminuria. Overall, our results do not support the routine prophylactic use of NAC as a free radical scavenger in abdominal surgery.

Topics: Abdomen; Acetylcysteine; Aged; Albuminuria; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Double-Blind Method; Female; Free Radical Scavengers; Humans; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Postoperative Period; Protein Precursors; Systemic Inflammatory Response Syndrome

To investigate whether short-term N-acetylcysteine (NAC) infusion administered before and during extensive abdominal surgery could modify the progression of early postoperative organ dysfunction and systemic inflammatory response.. After randomisation the treatment group (n = 47) received NAC (150 mg kg-1 bolus followed by a continuous infusion of 12 mg kg-1 h-1) and the placebo group (n = 46) received the same volume of 5% dextrose during surgery. Clinical progress was monitored by the Multiple organ dysfunction score, systemic inflammatory response by serum procalcitonin (PCT), C-reactive protein (CRP) and microalbuminuria during the first 3 postoperative days. Mann-Whitney and chi 2 tests were used for statistical analysis.. There was no significant difference between the two groups regarding the MODS, organ dysfunction, length of intensive care stay, days of mechanical ventilation and mortality. PCT and microalbuminuria did not differ significantly. Significantly lower CRP levels were found in the NAC group on day one and two [t24: median: 84.5 interquartile range: (62.48-120.25) vs. 118 (86-137) mg/l; p = 0.020; t48: 136 (103-232) vs. 195 (154.5-252) mg/l p = 0.013, NAC vs. placebo].. The results of this study do not support the routine use of NAC as a prophylactic drug during surgery, and reinforce previous evidence which challenge the indication of NAC in the critically ill patient.

Topics: Abdominal Neoplasms; Acetylcysteine; Aged; Albuminuria; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Double-Blind Method; Female; Humans; Inflammation; Infusions, Intravenous; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; Respiration, Artificial; Treatment Outcome

Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P < 0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P = 0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone.. In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids.

Topics: Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Disease Progression; Female; Hepatitis, Alcoholic; Humans; Lipopolysaccharides; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Protein Precursors; Retrospective Studies; Risk Assessment; Severity of Illness Index; Spain; Survival Analysis; Systemic Inflammatory Response Syndrome

To study the correlation between serum procalcitonin (PCT) level and severity of infant muggy syndrome (IMS) and the predictive value of PCT in the development of multiple organ dysfunction syndrome (MODS) in children with IMS.. Fifty children with IMS were classified into two groups according to the presence of MODS: MODS (n=29) and non-MODS (n=21). According to a 30-day follow-up result, they were classified into survival (n=36) and deceased groups (n=14). Vital signs, routine biological measurements (arterial blood gas, blood routine, CRP, liver and kidney functions, myocardial enzyme and so on) and the disease severity evaluated by the Pediatric Critical Illness Score (PCIS) within 24 hours of admission were recorded. Serum levels were measured using the semi-quantitative PCT-Q test within 24 hours of admission.. Forty-seven children (94%) had elevated serum PCT levels (≥ 0.5 ng/mL) at admission. There were lower PCIS scores, higher rates of MODS and higher levels of serum PCT in deceased patients than survivors (P<0.05). There was a significant negative correlation between serum PCT levels and PCIS scores (r=-0.84, P<0.05). Serum PCT levels in the MODS group were significantly higher than in the non-MODS group (P<0.01). Receiver operating characteristic curve showed that, if the cut-off point of serum PCT level was 10.6 ng/mL, the sensitivity and specificity of PCT were 79.3% and 90.5% respectively, in predicting MODS, with the area under the curve of 0.924 ( P<0.01).. Serum PCT level at admission is correlated with the severity of IMS and it may be an early predictive marker of MODS.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Infant; Infant, Newborn; Male; Multiple Organ Failure; Protein Precursors; Syndrome

Early identification of patients with infection and at risk of developing severe disease with organ dysfunction remains a difficult challenge. We aimed to evaluate and validate the heparin-binding protein, a neutrophil-derived mediator of vascular leakage, as a prognostic biomarker for risk of progression to severe sepsis with circulatory failure in a multicenter setting.. A prospective international multicenter cohort study.. Seven different emergency departments in Sweden, Canada, and the United States.. Adult patients with a suspected infection and at least one of three clinical systemic inflammatory response syndrome criteria (excluding leukocyte count).. None.. Plasma levels of heparin-binding protein, procalcitonin, C-reactive protein, lactate, and leukocyte count were determined at admission and 12-24 hours after admission in 759 emergency department patients with suspected infection. Patients were defined depending on the presence of infection and organ dysfunction. Plasma samples from 104 emergency department patients with suspected sepsis collected at an independent center were used to validate the results. Of the 674 patients diagnosed with an infection, 487 did not have organ dysfunction at enrollment. Of these 487 patients, 141 (29%) developed organ dysfunction within the 72-hour study period; 78.0% of the latter patients had an elevated plasma heparin-binding protein level (>30 ng/mL) prior to development of organ dysfunction (median, 10.5 hr). Compared with other biomarkers, heparin-binding protein was the best predictor of progression to organ dysfunction (area under the receiver operating characteristic curve=0.80). The performance of heparin-binding protein was confirmed in the validation cohort.. In patients presenting at the emergency department, heparin-binding protein is an early indicator of infection-related organ dysfunction and a strong predictor of disease progression to severe sepsis within 72 hours.

Topics: Adult; Aged; Antimicrobial Cationic Peptides; Area Under Curve; Biomarkers; Blood Proteins; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Canada; Carrier Proteins; Cause of Death; Cohort Studies; Critical Illness; Emergency Service, Hospital; Female; Hospital Mortality; Humans; Internationality; Male; Middle Aged; Multiple Organ Failure; Predictive Value of Tests; Prospective Studies; Protein Precursors; Risk Assessment; Sepsis; Survival Analysis; Sweden; Systemic Inflammatory Response Syndrome; Treatment Outcome; United States

Kynurenic acid (KYNA) is one of the end products of tryptophan metabolism. The aim of this study was to analyse plasma KYNA concentration in septic shock patients (SSP) with acute kidney injury (AKI) undergoing continuous veno-venous haemofiltration (CVVH). Changes in KYNA content were compared to alterations in the levels of procalcitonin (PCT), C-reactive protein and lactate. Adult SSP with AKI were examined. Measurements were conducted at seven time points: before beginning CVVH and at 6, 12, 24, 48, 72 and 96 h after the beginning of CVVH. Based on clinical outcomes, the data were analysed separately for survivors and non-survivors. Twenty-seven patients were studied. CVVH was associated with reduced plasma KYNA concentration only in survivors. Plasma KYNA concentration correlated with the levels of lactate and PCT only in survivors. (1) CVVH reduced plasma KYNA concentration only in survivors; (2) lack of this reduction may predict fatal outcomes in SSP.

Topics: Acute Kidney Injury; Bacterial Infections; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Hemofiltration; Humans; Kynurenic Acid; Lactic Acid; Male; Middle Aged; Multiple Organ Failure; Mycoses; Protein Precursors; Pyometra; Shock, Septic; Treatment Outcome; Urinary Tract Infections

Coagulation abnormalities which occur as a consequence of endothelial changes are recognized as diagnostic criteria for sepsis, but significance of these changes in the outcome prognosis and prediction of the course of sepsis is still not accurately defined.. 60 patients who fulfilled the criteria for diagnosis of sepsis were included in our study. Patients were categorized in two groups according to sepsis severity and organ failure and MODS development was assessed in the first 48 h from ICU admission. Prothrombin time (PT), activated partial thromboplastin time (aPTT) and endothelial cell specific molecule-1(endocan) levels, as well as procalcitonin (PCT) and C-reactive protein (CRP) were determined within the first 24h of the onset of the disease. Predictive APACHE II (Acute Physiology and Chronic Health Evaluation II) and SOFA (Sequential Organ Failure Assessment) scores were calculated on the day of ICU admission. Data were used to determine an association between day 1 biomarker levels, organ dysfunction score values and the development of organ failure, multiple organ dysfunction syndrome (MODS), and mortality during 28 days. These connections were determined by plotting of receiver operating characteristic (ROC) curves. Differences between groups were assessed by Mann-Whitney U test. Categorical variables were compared using chi-square test.. Concentration of endocan was significantly higher in the group of patients with sepsis induced organ failure, MODS development and in the group of non- survivors in contrast to group with less severe form of the disease, without multiorgan failure, and in contrast to group of survivors (p<0.05). Values of areas under the ROC curves showed that endocan levels had good discriminative power for more severe course of sepsis, MODS development and possible discriminative power for mortality prediction (AUC: 0.81, 0.67, 0.71 retrospectively), better than PCT for fatality (AUC:053) and better than APACHE II (AUC:0.55) and SOFA (AUC: 0.57) scores for organ failure.. Results of our study show that endocan can be used as strong and significant predictor of sepsis severity and outcome, perhaps even better than SOFA and APACHE II scores.

Topics: Adult; Aged; Aged, 80 and over; APACHE; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Chi-Square Distribution; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Neoplasm Proteins; Organ Dysfunction Scores; Partial Thromboplastin Time; Predictive Value of Tests; Prognosis; Protein Precursors; Proteoglycans; Prothrombin Time; Retrospective Studies; ROC Curve; Sepsis; Severity of Illness Index; Up-Regulation

To analyze the variation of serum insulin levels in critically ill children and investigate the underlying mechanism and clinical significance to provide the basis for treatment.. Totally 332 critically ill children admitted in pediatric intensive care unit (PICU) of Hunan Children's Hospital from Nov., 2011 to April, 2012 were studied. The high insulin group (n = 332) was defined as insulin levels within 24 h > 11.1 mU/L and was divided into 2 groups: mildly elevated group (n = 194): 11.10 - 33.30 mU/L, increased three times group (n = 138): > 33.3 mU/L. Insulin, C-peptide and blood glucose were measured within 24 hours after admission, on day 3 and 7. Other results of inflammatory markers, lactate, cardiac enzymes, amylase, pancreatic ultrasound, hepatic and renal function as well as indicators related to severity and prognosis were recorded after admission.. The peak of insulin level was seen on day 1, then presented a downward trend and reached the normal level on day 7. The peaks of blood glucose and C-peptide level were seen on day 1 then declined, the levels on day 7 were still slightly higher than normal level. The insulin level on admission (41.47 ± 30.85) mU/L were positively correlated with lactic acid (2.29 ± 1.81) mmol/L and procalcitonin level (5.08 ± 6.70) ng/ml (r = 0.370, P = 0.000; r = 0.168, P = 0.002) (P < 0.01). The insulin level on admission in children with 1 organ failure (41.24 ± 22.60) mU/L or 2 or multiple organ failure (48.98 ± 22.17) mU/L was higher than that in children with non-organ failure (34.11 ± 29.84) mU/L (U = 1621.001, P = 0.000;U = 1300.000, P = 0.000) (P < 0.01). The insulin level on admission in death group (52.99 ± 32.34) mU/L was higher than that in survival group (32.85 ± 24.10) mU/L (U = 1585.000, P = 0.000) (P < 0.01). Ten cases in death group were complicated with pancreatic damage and the average insulin level on admission was (65.29 ± 50.53) mU/L.. The high insulin level was correlated with the degree of inflammatory response, ischemia and hypoxia. The high insulin level in critically ill children was relevant to the pancreatic damage, the severity of the disease, organ dysfunction, and evaluation of prognosis.

Topics: Adolescent; Blood Glucose; C-Peptide; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Female; Humans; Infant; Infant, Newborn; Insulin; Intensive Care Units, Pediatric; Male; Multiple Organ Failure; Pancreas; Prognosis; Protein Precursors; Survival

Although absolute values for C-reactive protein (CRP) and procalcitonin (PCT) are well known to predict sepsis in the critically ill, it remains unclear how changes in CRP and PCT compare in predicting evolution of: infectious disease, invasiveness and severity (e.g. development of septic shock, organ failure and non-survival) in response to treatment. The current study attempts to clarify these aspects.. In 72 critically ill patients with new onset fever, CRP and PCT were measured on Day 0, 1, 2 and 7 after inclusion, and clinical courses were documented over a week with follow up to Day 28. Infection was microbiologically defined, while septic shock was defined as infection plus shock. The sequential organ failure assessment (SOFA) score was assessed.. From peak at Day 0-2 to Day 7, CRP decreased when (bloodstream) infection and septic shock (Day 0-2) resolved and increased when complications such as a new (bloodstream) infection or septic shock (Day 3-7) supervened. PCT decreased when septic shock resolved and increased when a new bloodstream infection or septic shock supervened. Increased or unchanged SOFA scores were best predicted by PCT increases and Day 7 PCT, in turn, was predictive for 28-day outcome.. The data, obtained during ICU-acquired fever and infections, suggest that CRP may be favoured over PCT courses in judging response to antibiotic treatment. PCT, however, may better indicate the risk of complications, such as bloodstream infection, septic shock, organ failure and mortality, and therefore might help deciding on safe discontinuation of antibiotics. The analysis may thus help interpreting current literature and design future studies on guiding antibiotic therapy in the ICU.

Topics: Adult; Aged; Bacteremia; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Disease Progression; Female; Fever; Humans; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Organ Dysfunction Scores; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Severity of Illness Index; Survival Analysis

Plasma concentration of procalcitonin (PCT) and its value in the diagnosis of infection in paediatric patients treated with extracorporeal membrane oxygenation (ECMO) are undefined. This study aimed to define the levels of PCT and C-reactive protein (CRP) in paediatric cardiac ECMO patients and to determine their role in predicting infection, severity of organ dysfunction and clinical outcome.. PCT and CRP plasma concentrations were measured daily in 20 consecutive infants and young children treated with veno-arterial ECMO. Each patient was examined daily for signs of infection and multiple organ dysfunction syndrome (MODS). A total of 139 patient days were classified for infection and MODS.. The median PCT and CRP plasma concentrations were not increased during infection: 2.4 vs 8.8 ng/ml and 223.8 vs 240.6 mg/l, in patients with vs without infection, respectively. PCT, but not CRP, was significantly elevated during MODS (10.9 vs 1.85 ng/ml) (P = 0.001). The area under the receiver operating characteristic (ROC) curve was 0.984 for PCT (95% confidence interval [CI], 0.962-1.000) compared with 0.347 for CRP (95% CI, 0.211-0.484) (P = 0.001). Only PCT differed significantly in patients weaned from ECMO who survived (2.6 ng/ml) vs patients not weaned from ECMO (10.5 ng/ml) (P = 0.001). The area under the ROC curve was 0.871 (95% CI, 0.786-0.956) compared with 0.261 for CRP (95% CI, 0.145-0.377) (P = 0.001).. Neither PCT nor CRP are reliable markers of infection in paediatric cardiac ECMO patients. However, high levels of PCT are associated with MODS. PCT may be used as a prognostic indicator of clinical outcome in this high-risk population.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Extracorporeal Membrane Oxygenation; Female; Humans; Infant; Infant, Newborn; Infections; Linear Models; Male; Multiple Organ Failure; Protein Precursors; ROC Curve; Sepsis; Statistics, Nonparametric; Treatment Outcome

To evaluate procalcitonin clearance as a prognostic biomarker in septic shock.. Prospective, observational pilot study.. Intensive care unit.. Patients admitted to the ICU due to septic shock and multiorgan dysfunction.. Serum concentrations of procalcitonin were determined within 12h of onset of septic shock and multiorgan dysfunction (coinciding with admission to the ICU), and the following extractions were obtained after 24, 48 and 72h in patients who survived.. Demographic data, Acute Physiology and Chronic Health Evaluation II score, and Sequential Organ Failure Assessment score, data on the primary focus of infection, and patient outcome (ICU mortality).. Procalcitonin clearance was higher in survivors than in non-survivors, with significant differences at 24h (73.9 [56.4-83.8]% vs 22.7 [-331-58.4], p<0.05) and 48h (81.6 [71.6-91.3]% vs -7.29 [-108.2-82.3], p<0.05). The area under the ROC curve was 0.74 (95%CI, 0.54-0.95, p<0.05) for procalcitonin clearance at 24h, and 0.86 (95%CI, 0.69-1.0, p<0.05) at 48h.. ICU mortality was associated to sustained high procalcitonin levels, suggesting that procalcitonin clearance at 48h may be a valuable prognostic biomarker.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Multiple Organ Failure; Pilot Projects; Prognosis; Prospective Studies; Protein Precursors; Shock, Septic

To investigate the value of procalcitonin (PCT) in the early diagnosis and risk stratification in sepsis.. Among 90 patients, 42 patients suffered sepsis, and 48 patients with severe sepsis. Serum PCT levels, high sensitivity C-reactive protein (hs-CRP), white blood cell (WBC) count, the percentage of neutrophils and lactate levels in sepsis and severe sepsis patients were determined. Receive operating characteristic curve (ROC curve) was drawn to evaluate the ability of PCT and related inflammatory parameters in assessing risk factors in patients with sepsis, and to analyze correlation between PCT and sequential organ failure assess (SOFA) score, WBC, lactic acid, and hs-CRP.. Compared with sepsis patients, among severe sepsis patients, the levels of PCT (μg/L), hs-CRP (mg/L), WBC [×10(9)/L] , and SOFA score were significantly higher (PCT: 7.228±2.153 vs. 0.172±0.165, hs-CRP: 102.68±90.99 vs. 29.05±28.76, WBC: 14.15±8.14 vs. 8.15±4.55, SOFA score: 9.87±2.47 vs. 3.09±1.55), with statistical significance (all P<0.01), and the levels of percentage of neutrophils and lactic acid (mmol/L) were slightly increased (percentage of neutrophils: 0.820±0.094 vs. 0.740±0.130, lactic acid: 1.47±0.99 vs. 1.18±0.60), with no statistical significance (both P>0.05). Analysis of ROC curve displayed that area under the curve (AUC) of PCT was 0.808, which was higher than that of WBC, percentage of neutrophils, lactic acid and hs-CRP (AUC was 0.124, 0.042, 0.551 and 0.262, respectively), and when PCT was 1.000 μg/L, the sensitivity was 80.3%, specificity was 72.2%, and they were better than those of other traditional markers of inflammation. Bivariate correlation analysis showed that a positive correlation was found between PCT and SOFA score and WBC [r1=0.418, P1=0.006; r2=0.251, P2=0.011], and there was no correlation between PCT and lactic acid and hs-CRP [r1=0.186, P1=0.155; r2=0.089, P2=0.133].. Serum PCT is a reliable measure in emergency room for early diagnosis of sepsis with high sensitivity and specificity, it could be used as a routine monitoring index in critically ill patients to help assess disease severity in sepsis.

Topics: Aged; Aged, 80 and over; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Early Diagnosis; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Protein Precursors; Sepsis; Severity of Illness Index

Multiorgan dysfunction syndrome represents a continuum of cumulative organ dysfunction from very mildly altered function to total and, rarely, irreversible organ failure and is the major cause of death in the intensive care unit (ICU). The terms multiple organ failure syndrome (MOFS), multiple organ system failure (MOSF), and multiple organ failure (MOF) have since been used to describe this syndrome. Infections were initially thought to be the main cause of multiorgan dysfunction; however, other insults, such as severe trauma, burn injuries, and noninfectious inflammatory diseases may precipitate a similar condition. In 2001, several North American and European intensive care societies revisited the definitions for sepsis and related conditions. Additional criteria indicative of physiological derangements were added to the traditional systemic inflammatory response syndrome (SIRS) criteria, including clinical abnormalities (altered mental status, ileus) and biochemical evidence of a sepsis response [procalcitonin (PCT), C-reactive protein (CRP), creatinine, or cytokine levels]. The use of organ failure scores to describe organ dysfunction in ICU patients was encouraged. The pulmonary, cardiovascular, renal, hepatic, hematologic, and central nervous systems are the organs most commonly considered when describing organ dysfunction/failure in the ICU. Scoring systems for organ dysfunction/failure were designed primarily as descriptive tools, aimed at establishing standardized definitions to stratify and compare patients in the ICU in terms of morbidity rather than mortality. Sequential evaluation of organ dysfunction during the ICU stay may track disease progression and may be useful prognostically. We discuss the various scoring systems developed over the past 2 decades and present a rational approach to their role in assessing and following critically ill patients.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Creatinine; Critical Illness; Cytokines; Disease Progression; Humans; Intensive Care Units; Multiple Organ Failure; Prognosis; Protein Precursors; Sepsis

We evaluated the performance of procalcitonin (PCT) and C-reactive protein (CRP) threshold values and kinetics as predictors of ventilator-associated pneumonia (VAP) survival and septic shock development. 45 adult patients with VAP were studied. Serum CRP and PCT levels and the Sequential Organ Failure Assessment (SOFA) score were measured on days 1, 4 and 7 (D1, D4, D7) of VAP and their variations between different days (kinetics) were calculated (DeltaPCT, DeltaCRP). A multivariate logistic regression model was constructed with either VAP 28-day survival or septic shock development as dependent variables, and PCT values, CRP values, kinetics, age, sex, SOFA and Acute Physiology and Chronic Health Evaluation (APACHE) II score as independent variables. No difference was found in CRP levels between survivors and nonsurvivors. Nonsurvivors had significantly higher PCT levels on D1 and D7. In the multivariate analysis, the only factors predicting VAP survival were DeltaPCT(7-1) (OR 7.23, 95% CI 0.008-0.468) and DeltaCRP(7-4) (OR 4.59, 95% CI 0.013-0.824). VAP patients who developed septic shock had significantly higher CRP levels on D1 and D7 and higher PCT levels on D1 and D4. The only factor predicting the development of septic shock was SOFA on D1 (OR 7.44, 95% CI 1.330-5.715). Neither PCT and CRP threshold values nor their kinetics can predict VAP survival or septic shock development.

Topics: Adult; Aged; APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Intensive Care Units; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Pneumonia; Predictive Value of Tests; Protein Precursors; Respiration, Artificial; Shock, Septic

Despite recent advances in treatment of severe injured patients, e.g. due to damage control orthopaedics, multi organ dysfunction syndrome (MODS) and sepsis are major complications in daily practice. During one year 94 patients were prospectively collected.. ISS 16, age 18-60 y, primary admission to our level-1 trauma center, survival > 48 hours after trauma. The development of MODS and sepsis were observed and different groups were formed (+/-). Demographic data revealed no significant differences between the subgroups. Comparing groups +MODS and -MODS significant differences on admission day were observed, when PCT showed first on day 2 after trauma differences. Regarding the development of sepsis PCT was advantageous to IL-6 showing significant higher plasma levels in group +sepsis from the first day after trauma. Serum levels of IL-6 and PCT could be useful in early identification of high risk patients to develop posttraumatic MODS. For sepsis PCT is the better prognostic factor.

Topics: Adolescent; Adult; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Female; Humans; Injury Severity Score; Interleukin-6; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Predictive Value of Tests; Prognosis; Prospective Studies; Protein Precursors; Sepsis; Systemic Inflammatory Response Syndrome; Young Adult

The diagnosis of adult onset Still's disease is difficult in the absence of definite clinical and laboratory criteria. A delayed diagnosis of adult onset Still's disease was made in a 23-year-old female who developed multi-organ failure and disseminated intravascular coagulation with fingertip auto-amputation during a febrile illness considered septic due to the persistence of elevated serum procalcitonin concentration.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Disseminated Intravascular Coagulation; Female; Humans; Multiple Organ Failure; Protein Precursors; Shock, Septic; Still's Disease, Adult-Onset; Young Adult

Procalcitonin (PCT) is accepted to be a relevant prognostic marker for the development of clinical complications in multiple trauma patients. Therefore, a prospective cohort study was conducted to investigate whether polymorphisms in the calcitonin (CALCA) gene are associated with PCT levels and posttraumatic complications.. During a 14day observation period, blood samples were drawn once daily for systemic PCT concentrations in multiple trauma patients (Injury Severity Score >16). For analysis of allele frequencies, genotype distribution and PCT concentrations polytraumatized patients were separated, according to the development of SIRS, sepsis, septic shock, ARDS, MODS and mortality. Furthermore, association between CALCA polymorphisms and PCT plasma concentrations was assessed.. One hundred thirty seven patients with a mean ISS of 29.2+/-12.1 were included. When trauma patients were grouped according to different posttraumatic complications no association with CALCA SNPs was observed. Additionally, no association was found between CALCA polymorphisms and systemic PCT levels.. CALCA polymorphisms are unlikely to influence clinical outcome in polytraumatized patients. Effects of microbial and inflammatory mediators, as well as other risk factors (gender, age, etc.) seem to have a more significant influence on the transcriptional regulation of CALCA and on PCT plasma concentrations than CALCA polymorphisms.

Topics: Adult; Calcitonin; Calcitonin Gene-Related Peptide; Female; Gene Frequency; Genotype; Haplotypes; Humans; Male; Middle Aged; Multiple Organ Failure; Multiple Trauma; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Prognosis; Protein Precursors; Respiratory Distress Syndrome; Sepsis; Shock, Septic; Systemic Inflammatory Response Syndrome; Young Adult

Methods for lipopolysaccharide (LPS) (endotoxin) reduction have been proposed as one way to improve the treatment of Gram-negative sepsis. Here we present a case with severe Gram-negative sepsis, treated with a novel device for LPS adsorption (Alteco LPS Adsorber, Alteco Medical AB, Lund, Sweden). After LPS adsorption, the level of LPS in the patient's bloodstream was almost eliminated: from 1.44 EU/ml before treatment to 0.03 EU/ml post treatment). The procalcitonin level and inflammatory cytokines were concurrently reduced. Also, an obvious improvement in the status of the patient's hemodynamics was seen. Forty-five days after treatment the patient is still alive. In conclusion, LPS adsorption may represent a significant improvement in the treatment of Gram-negative sepsis and further studies are planned.

Topics: Abdomen; Acute Disease; Adsorption; Adult; Anticoagulants; Calcitonin; Calcitonin Gene-Related Peptide; Cholecystectomy; Hemoperfusion; Hemorrhage; Heparin; Humans; Lipopolysaccharides; Male; Multiple Organ Failure; Pancreatitis, Acute Necrotizing; Protein Precursors; Pseudomonas aeruginosa; Renal Insufficiency; Respiratory Insufficiency; Sepsis; Severity of Illness Index; Treatment Outcome

To investigate plasma high-mobility group box 1 protein (HMGB1) concentration and its relationship with organ dysfunction and outcome in septic shock patients.. Prospective, noninterventional study. Medical adult intensive care unit at a university hospital in France.. 42 critically ill patients with septic shock.. Arterial blood was drawn within 12 h of admission for the measurement of plasma HMGB1 concentration by ELISA. Repeated sampling was performed on days 3, 7, and 14.. Median HMGB1 concentration was 4.4 ng/ml (IQR 1.2-12.5) at admission, with no difference between survivors and nonsurvivors. A positive correlation was observed between HMGB1 and SOFA score and lactate, and procalcitonin concentrations. There was a progressive but statistically nonsignificant decline in HMGB1 concentration among the survivors, while nonsurvivors showed an increase in HMGB1 level between days 1 and 3. SOFA score and lactate and procalcitonin concentrations did not vary significantly between days 1 and 3. When measured on day 3, HMGB1 discriminated survivors from nonsurvivors with 66% sensitivity and 67% specificity, and concentration greater than 4 ng/ml was associated with an odds ratio of death of 5.5 (95% CI 1.3-23.6).

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Enzyme-Linked Immunosorbent Assay; Female; France; HMGB1 Protein; Humans; Inflammation; Intensive Care Units; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; Shock, Septic

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Glycoproteins; Humans; Multiple Organ Failure; Peritonitis; Prognosis; Protein Precursors

Identification of postoperative patients at high risk of dying early after intensive care unit (ICU) admission through a fast and readily available parameter may help in determining therapeutic interventions or further diagnostic procedures that could have an impact on patients' outcome. The aim of our study was to assess the utility of procalcitonin (PCT) and other readily available parameters, as useful early (days 1-3) predictors of mortality in postoperative patients diagnosed with severe sepsis within 24 h preceding their operation.. More than a period of 2 yr, subsets of 69 postoperative patients admitted with severe sepsis and 890 non-septic ICU patients were investigated. PCT, C-reactive protein (CRP) and sequential organ failure assessment (SOFA) score were recorded over the duration of ICU stay.. PCT area under receiver operating characteristic (ROC) curve was 0.78 on day 3 and was highly predictive of fatal outcome (0.90) at day 6. Area under ROC curve of SOFA score was 0.85 on day 3 and remained in this range until day 6. Area under ROC curves on day 3 of CRP (0.61) was non-predictive and remained non-predictive over the duration of ICU stay.. PCT exhibited no discriminative power early after ICU admission for prediction of mortality in critically ill patients with severe sepsis, compared with a high predictive power of SOFA score on day 3. However, using PCT could still serve as a useful complementary comparator for prediction of survival outcome using the SOFA score.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Critical Illness; Female; Humans; Length of Stay; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Prognosis; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Survival Analysis

To investigate day-by-day changes in procalcitonin and maximum obtained levels as predictors of mortality in critically ill patients.. Prospective observational cohort study.. : Multidisciplinary intensive care unit at Rigshospitalet, Copenhagen University Hospital, a tertiary reference hospital in Denmark.. Four hundred seventy-two patients with diverse comorbidity and age admitted to this intensive care unit.. Equal in all patient groups: antimicrobial treatment adjusted according to the procalcitonin level.. Daily procalcitonin measurements were carried out during the study period as well as measurements of white blood cell count and C-reactive protein and registration of comorbidity. The primary end point was all-cause mortality in a 90-day follow-up period. Secondary end points were mortality during the stay in the intensive care unit and in a 30-day follow-up period. A total of 3,642 procalcitonin measurements were evaluated in 472 critically ill patients. We found that a high maximum procalcitonin level and a procalcitonin increase for 1 day were independent predictors of 90-day all-cause mortality in the multivariate Cox regression analysis model. C-reactive protein and leukocyte increases did not show these qualities. The adjusted hazard ratio for procalcitonin increase for 1 day was 1.8 (95% confidence interval 1.3-2.7). The relative risk for mortality in the intensive care unit for patients with an increasing procalcitonin was as follows: after 1 day increase, 1.8 (95% confidence interval 1.4-2.4); after 2 days increase, 2.2 (95% confidence interval 1.6-3.0); and after 3 days increase: 2.8 (95% confidence interval 2.0-3.8).. A high maximum procalcitonin level and a procalcitonin increase for 1 day are early independent predictors of all-cause mortality in a 90-day follow-up period after intensive care unit admission. Mortality risk increases for every day that procalcitonin increases. Levels or increases of C-reactive protein and white blood cell count do not seem to predict mortality.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Critical Illness; Denmark; Female; Humans; Infant; Leukocyte Count; Male; Middle Aged; Multiple Organ Failure; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Survival Analysis

Topics: Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Illness; Denmark; Humans; Multiple Organ Failure; Prognosis; Protein Precursors; Sepsis

To study the correlation between serum procalcitonin (PCT) level and severity of multiple organ dysfunction syndrome (MODS).. Sixty-one patients with MODS were enrolled in this study. They were divided into infection group and non-infection group. Serum PCT were measured using an immunoluminometric assay. Acute physiology and chronic health evaluation II (APACHE II) scores and Marshall scores of the two groups were recorded and the relationship between PCT levels and APACHE II scores as well as Marshall scores was analysed.. Serum PCT levels in patients with MODS were higher. Serum PCT [13.01(2.73, 64.79) microg/L], APACHE II [(17.50+/-5.35) scores] and Marshall score [(6.38+/-2.46) scores] of infection group were significantly higher than non-infection group [1.50 (0, 2.98) microg/L, (14.67+/-3.01) scores, and (4.62+/-2.01) scores, respectively, P<0.05 or P<0.001]. Serum PCT of infection group and non-infection group did not show correlation with APACHE II (r=0.175, P=0.281; r=0.071, P=0.759). Serum PCT of all patients with MODS showed positive correlation with Marshall score (r=0.514, P<0.001), and correlation index of infection group was higher (r=0.535, P<0.001). Serum PCT of non-infection group did not show correlation with Marshall score (r=0.003, P=0.991).. Serum PCT has clinical values in judgment of the severity of infected patients complicated by MODS.

Topics: Adult; Aged; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Middle Aged; Multiple Organ Failure; Protein Precursors; Young Adult

Procalcitonin (PCT) is a newly introduced marker of systemic inflammation and bacterial infection. A marked increase in circulating PCT level in critically ill patients has been related with the severity of illness and poor survival. The goal of this study was to compare the prognostic power of PCT and three other parameters, the arterial ketone body ratio (AKBR), the acute physiology, age, chronic health evaluation (APACHE) III score and the multiple organ dysfunction score (MODS), in the differentiation between survivors and nonsurvivors of systemic inflammatory response syndrome (SIRS). The study was performed in 95 patients over 16 years of age who met the criteria of SIRS. PCT and AKBR were assayed in arterial blood samples. The APACHE III score and MODS were recorded after the first 24 hours of surgical ICU (SICU) admission and then daily for two weeks or until either discharge or death. The patients were divided into two groups, survivors (n=71) and nonsurvivors (n=24), in accordance with the ICU outcome. They were also divided into three groups according to the trend of PCT level: declining, increasing or no change. Significant differences between survivors and nonsurvivors were found in APACHE III score and MODS throughout the study period, but in PCT value only up to the 7th day and in AKBR only up to the 3rd day. PCT values of the three groups were not significantly different on the first day between survivors and nonsurvivors. Receiver operating characteristic (ROC) curves for prediction of mortality by PCT, AKBR, APACHE III score and MODS were 0.690, 0.320, 0.915 and 0.913, respectively, on the admission day. In conclusion, PCT could have some use as a mortality predictor in SIRS patients but was less reliable than APACHE III score or MODS.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Ketone Bodies; Male; Middle Aged; Multiple Organ Failure; Predictive Value of Tests; Protein Precursors; Survival Analysis; Systemic Inflammatory Response Syndrome

Both C-reactive protein (CRP) and procalcitonin (PCT) are accepted sepsis markers. However, there is still some debate concerning the correlation between their serum concentrations and sepsis severity. We hypothesised that PCT and CRP concentrations are different in patients with infection or with no infection at a similar severity of organ dysfunction or of systemic inflammatory response.. One hundred and fifty adult intensive care unit patients were observed consecutively over a period of 10 days. PCT, CRP and infection parameters were compared among the following groups: no systemic inflammatory response syndrome (SIRS) (n = 15), SIRS (n = 15), sepsis/SS (n = 71) (including sepsis, severe sepsis and septic shock [n = 34, n = 22 and n = 15]), and trauma patients (n = 49, no infection).. PCT and CRP concentrations were higher in patients in whom infection was diagnosed at comparable levels of organ dysfunction (infected patients, regression of median [ng/ml] PCT = -0.848 + 1.526 sequential organ failure assessment [SOFA] score, median [mg/l] CRP = 105.58 + 0.72 SOFA score; non-infected patients, PCT = 0.27 + 0.02 SOFA score, P < 0.0001; CRP = 84.53 - 0.19 SOFA score, P < 0.005), although correlation with the SOFA score was weak (R = 0.254, P < 0.001 for PCT, and R = 0.292, P < 0.001 for CRP). CRP levels were near their maximum already during lower SOFA scores, whereas maximum PCT concentrations were found at higher score levels (SOFA score > 12).PCT and CRP concentrations were 1.58 ng/ml and 150 mg/l in patients with sepsis, 0.38 ng/ml and 51 mg/l in the SIRS patients (P < 0.05, Mann-Whitney U-test), and 0.14 ng/ml and 72 mg/l in the patients with no SIRS (P < 0.05). The kinetics of both parameters were also different, and PCT concentrations reacted more quickly than CRP.. PCT and CRP levels are related to the severity of organ dysfunction, but concentrations are still higher during infection. Different sensitivities and kinetics indicate a different clinical use for both parameters.

Topics: Adult; Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Intensive Care Units; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Systemic Inflammatory Response Syndrome

The procalcitonin (PCT) level in the blood was determined in cases of acute pancreatitis. The PCT level was found to show a significant correlation with the severity of acute pancreatitis. Furthermore, the PCT level was significantly higher in the cases which developed MODS than in those which did not. The PCT level was significantly higher in the patients who eventually died than in those who survived. A significant correlation was observed between the serum PCT level and the serum tumor necrosis factor alpha level. Thus, PCT level was found to be a reliable indicator of the severity of acute pancreatitis.

Topics: Acute Disease; Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Protein Precursors; Severity of Illness Index; Tumor Necrosis Factor-alpha

To investigate the correlation between microalbuminuria and extravascular lung water in patients in septic shock who require mechanical ventilation for severe respiratory failure.. Prospective, observational, clinical study in the 20-bed intensive care unit of a university hospital.. 25 consecutive patients in septic shock and also in severe respiratory failure requiring mechanical ventilation.. Hemodynamic parameters and extravascular lung water were determined by single arterial thermodilution. Together with each hemodynamic measurement the PaO(2)/FIO(2) ratio and urinary microalbumin to creatinine ratio (M:Cr) was measured. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were also determined daily.. The EVLW index was significantly higher than normal throughout the study. Microalbuminuria was in the normal range on entry and remained so for the rest of the study period. Serum PCT and CRP levels were significantly higher than normal at every assessment points. No significant correlation was found between M:Cr and either EVLW or PaO(2)/FIO(2).. In this study patients in septic shock with significantly elevated EVLW had normal urinary M:Cr, and there was no correlation between M:Cr and EWLV, and PaO(2)/FIO(2). Therefore based on the current results routine measurements of microalbuminuria to determine endothelial permeability cannot be recommended in critically ill patients.

Topics: Aged; Albuminuria; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Capillary Permeability; Creatinine; Extravascular Lung Water; Female; Hemodynamics; Humans; Linear Models; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; Respiration, Artificial; Respiratory Insufficiency; Shock, Septic; Statistics, Nonparametric; Thermodilution

Cardiopulmonary bypass is often associated with pathophysiological changes in form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). In the present study, we investigated plasma levels of pro- and anti-inflammatory cytokines in survivors and non-survivors from MODS in the early postoperative course following open heart surgery.. Prospective clinical study.. A University Cardiothoracic Intensive Care Unit.. Levels of cytokines (IL-6, IL-8, IL-10, IL-18, and TGF- ) and procalcitonin (PCT) were measured at the first four postoperative days in 16 adult male patients with an Apache II-score >24 and two or more organ dysfunctions after myocardial revascularization.. All pro-inflammatory cytokines, except for IL-6, were significantly elevated in non-survivors from MODS, with peak values at the first two postoperative days. The plasma levels of immunoinhibitory cytokines showed no differences between the groups.. The results of our study show a different expression of pro-inflammatory cytokines in survivors and non-survivors from MODS following operations with extracorporeal circulation. In addition to Apache-II score, especially IL-8, IL-18, and PCT may be used as parameters for the prognosis of patients with organ dysfunctions after cardiac surgery.

Topics: Aged; APACHE; Calcitonin; Calcitonin Gene-Related Peptide; Cardiopulmonary Bypass; Cytokines; Hospitals, University; Humans; Male; Multiple Organ Failure; Myocardial Revascularization; Postoperative Complications; Prospective Studies; Protein Precursors; Survival Rate; Systemic Inflammatory Response Syndrome

To examine the relationships between procalcitonin, bacterial infection, sepsis-induced multiple organ failure, and mortality rate in children.. Cohort study.. A multidisciplinary, tertiary-care pediatric intensive care unit.. Seventy-eight children meeting criteria for sepsis or septic shock and 12 critically ill children without sepsis.. Venous or arterial blood sampling.. Demographic, epidemiologic, and outcome data were recorded. Plasma from children with sepsis were collected on days 1 and 3, and procalcitonin concentrations were measured by immunoluminometric assay. Organ failure index scores were determined, and multiple organ failure was defined as organ failure index > or = 3. Persistent multiple organ failure was defined by presence of multiple organ failure on day 3. Procalcitonin concentrations (median [25th percentile-75th percentile]) were increased among children with sepsis on day 1 (2.4 ng/mL [0.2-24.2], p < .01) but not on day 3 (0.8 ng/mL [0.1-8.1], p = nonsignificant) vs. controls (0.2 ng/mL [0.1-0.5]). This increase in procalcitonin concentration was particularly robust among children with bacterial sepsis on day 1 (7.1 ng/mL [0.9-44.8], p < .001) and on day 3 (2.9 ng/mL [0.1-32.4], p < .05). Procalcitonin concentrations were not increased among children with fungal, viral, or culture-negative sepsis vs. controls. Procalcitonin concentrations were persistently increased over time among patients with bacterial sepsis who had persistent multiple organ failure (p < .05) and who died (p < .01) but not among patients with nonbacterial sepsis.. Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis. Further study is needed to better delineate this differential procalcitonin response to bacterial vs. nonbacterial sepsis and to characterize any mechanistic role that procalcitonin might play in the development of bacterial sepsis-induced multiple organ failure and mortality.

Topics: Adolescent; Analysis of Variance; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Intensive Care Units, Pediatric; Male; Multiple Organ Failure; Protein Precursors; Sepsis; Shock, Septic

Topics: Adolescent; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Critical Care; Humans; Infant; Intensive Care Units, Pediatric; Multiple Organ Failure; Prognosis; Protein Precursors; Sepsis

To compare the clinical informative value of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations in the detection of infection and sepsis and in the assessment of severity of sepsis.. Prospective study.. Medicosurgical intensive care unit.. Seventy consecutive adult patients who were admitted to the intensive care unit for an expected stay >24 hrs.. None.. PCT and CRP plasma concentrations were measured daily during the intensive care unit stay. Each patient was examined daily for signs and symptoms of infection and was classified daily in one of the following four categories according to the American College of Chest Physicians/Society of Critical Care Medicine criteria: negative, systemic inflammatory response syndrome, localized infection, and sepsis group (sepsis, severe sepsis, or septic shock). The severity of sepsis-related organ failure was assessed by the sepsis-related organ failure assessment score.. A total of 800 patient days were classified into the four categories. The median plasma PCT concentrations in noninfected (systemic inflammatory response syndrome) and localized-infection patient days were 0.4 and 1.4 ng/mL (p <.0001), respectively; the median CRP plasma concentrations were 79.9 and 85.3 mg/L (p =.08), respectively. The area under the receiver operating characteristic curve was 0.756 for PCT (95% confidence interval [CI], 0.675-0.836), compared with 0.580 for CRP (95% CI, 0.488-0.672) (p <.01). The median plasma PCT concentrations in nonseptic (systemic inflammatory response syndrome) and septic (sepsis, severe sepsis, or septic shock) patient days were 0.4 and 3.65 ng/mL (p <.0001), respectively, whereas those for CRP were 79.9 and 115.6 mg/L (p <.0001), respectively. The area under the receiver operating characteristic curve was 0.925 for PCT (95% CI, 0.899-0.952), compared with 0.677 for CRP (95% CI, 0.622-0.733) (p <.0001). The linear correlation between PCT plasma concentrations and the four categories was much stronger than in the case of CRP (Spearman's rho, 0.73 vs. 0.41; p <.05). A rise in sepsis-related organ failure assessment score was related to a higher median value of PCT but not CRP.. PCT is a better marker of sepsis than CRP. The course of PCT shows a closer correlation than that of CRP with the severity of infection and organ dysfunction.

Topics: Aged; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Humans; Multiple Organ Failure; Prospective Studies; Protein Precursors; ROC Curve; Sepsis; Severity of Illness Index; Statistics, Nonparametric; Systemic Inflammatory Response Syndrome

We prospectively evaluated the capacity of serum procalcitonin (PCT), compared with serum levels of C-reactive protein (CRP) and endotoxin, to identify children at high risk for mortality from sepsis after BMT. Of 47 pediatric bone marrow transplantation patients studied, 22 had an uneventful course post-transplant (Group 1), 17 survived at least one septic event (Group 2), and eight died from multiorgan failure (MOF) following septic shock (Group 3). Median concentrations of PCT over the course of the study were 1.3, 15.2, and 102.8 ng/ml, respectively, in each of the three groups (P<0.002 for each comparison). Median concentrations of CRP were 91, 213, and 260 mg/l, respectively (P<0.001 for Group 1 vs Group 2 and Group 3; P=NS for Group 2 vs Group 3). Median concentrations of endotoxin were 0.21, 0.30, and 0.93 U/l, respectively (P=NS for each comparison). Median concentrations of PCT, in contrast to serum CRP and endotoxin, correlated with the severity of sepsis (8.2 ng/ml in 'sepsis' and 22.3 ng/ml in 'severe sepsis', P=0.028) and provided useful prognostic information during septic episodes.

Topics: Adolescent; Adult; Bone Marrow Transplantation; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Endotoxins; Female; Germany; Humans; Infant; Male; Multiple Organ Failure; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Sepsis; Shock, Septic

PCT is a new highly sensitive and specific marker of bacterial and fungi infection--to be used in differential diagnosis at Infectious Diseases Departments. Author in this paper presents structure and mechanism of stimulation of PCT as a factor of "early infection's fase" for many infectious agents: bacteria, fungi, viruses and parasites. PCT may be found useful in diagnosing diseases; for ex.: sepsis, meningitis, inflammation of respiratory system, spontaneous bacterial peritonitis (SPB) and other local inflammatory foci (otitis media, endocarditis). PCT level is low in systemic inflammatory response syndrome (SIRS) and multiorgan dysfunction syndrome (MODS) of non-infectious origin (< 0.5 ng/ml), medium in case of localized infections (1.0-2.0 ng/ml) and in severe cases of disseminated infections (sepsis-->SIRS-->MODS) high (approximately 20 ng/ml).

Topics: Bacterial Infections; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Central Nervous System Infections; Diagnosis, Differential; Endocarditis, Bacterial; Humans; Multiple Organ Failure; Mycoses; Parasitic Diseases; Peritonitis; Protein Precursors

We examined whether procalcitonin (PCT) or neopterin (NT) are useful in predicting sepsis, multiple organ failure (MOF), or death after multiple trauma (MT). In a prospective clinical study, a total of 137 consecutive trauma patients (mean age 39 years, median injury severity score [ISS] 27 points) and 34 healthy volunteers were enrolled. Blood samples were collected on arrival in the emergency room until day 28 after trauma. Plasma NT was detected by enzyme-linked immunoassay and PCT plasma levels were determined using an immunoluminometric assay. The incidence of sepsis was 65%, MOF 48%, and death in hospital within 28 days 11%. After adjustment for age, gender, and ISS, PCT and NT levels during the first 2 days after injury were unable to differentiate between patients who developed sepsis or not. On the contrary, patients who developed MOF had higher PCT plasma levels on day 0 (0.60 vs. 0.15 ng/mL), and on days 1 and 2 combined (1.95 vs. 0.32 ng/mL). This difference remained significant in multivariate logistic regression (P = 0.01) and additional subgroup analyses for early and late MOF (P = 0.048 and 0.002). For NT, smaller differences were observed (4.39 vs. 3.68 nmol/L, and 7.20 vs. 5.79 nmol/L), which lost significance in multivariate analysis. On the basis of PCT, ISS, and age, a MOF prediction rule was developed and had a good predictive power (area under the curve: 0.77; P < 0.001). These findings demonstrate that high plasma concentrations of PCT in the early posttraumatic phase are an independent predictor of MOF but not of sepsis.

Topics: Abbreviated Injury Scale; Adult; Age Factors; Analysis of Variance; Area Under Curve; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Injury Severity Score; Logistic Models; Male; Middle Aged; Models, Statistical; Multiple Organ Failure; Neopterin; Predictive Value of Tests; Protein Precursors; ROC Curve; Sensitivity and Specificity; Sepsis; Wounds and Injuries

Topics: Abdomen; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Humans; Multiple Organ Failure; Postoperative Complications; Prognosis; Protein Precursors

The prognostic value of elevated serum levels of procalcitonin (PCT) in patients early after cardiac surgery on cardiopulmonary bypass (CPB) remains unclear. In a prospective study, we investigated whether PCT is useful as a prognostic marker in cardiac surgery with respect to mortality, complications and infections, and whether PCT is a specific marker for occurrence of infections.. Within 8 months, a subset of 80 high-risk patients (APACHE II-score: 25.1 +/- 4.7 (mean +/- SD)) out of a consecutive cohort of 776 patients was investigated. Demographic data, operative data and clinical endpoints (mortality, infection, severe complication) were documented. Serum levels of PCT were analyzed preoperatively and at postoperative day 1.. Hospital mortality in this high-risk group was 21.3 %, infections occurred in 33.8 % and complications in 58.8 % of the patients. Preoperative PCT was normal in all patients. Postoperative PCT was increased in non-survivors compared to survivors (34.3 +/- 7.0 ng/ml vs. 15.9 +/- 4.9 ng/ml; p < 0.05), in patients with severe complications (30.3 +/- 6.7 ng/ml vs. 5.5 +/- 1.4 ng/ml; p < 0.05) and in patients with infections (38.4 +/- 11.3 ng/ml vs. 10.8 +/- 1.6 ng/ml; p < 0.05). Area under receiver operating characteristic curve for PCT as predictor of mortality, infections and complications was 0.772 (95 %-confidence-interval (CI): 0.651 - 0.894), 0.720 (95 %-CI: 0.603 - 0.837) and 0.861 (95 %-CI: 0.779 - 0.943), respectively. PCT was not different with infectious compared to non-infectious complications.. High levels of PCT are associated with mortality, infections, and severe complications early after cardiac surgery using cardiopulmonary bypass and therefore provide a valuable prognostic marker. However, PCT does not discriminate between infectious and non-infectious complications.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Female; Glycoproteins; Humans; Male; Mediastinitis; Multiple Organ Failure; Pneumonia; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis

To evaluate plasma amino acid concentrations and markers of inflammation in the early stage and the course of septic encephalopathy.. Prospective, case series of patients with well-defined septic encephalopathy.. Surgical department and intensive care unit of a university hospital.. Seventeen patients with sepsis according to the ACCP/SCCM consensus conference criteria and encephalopathy based on neuropsychological tests, compared to a control group undergoing uncomplicated thoracic surgery.. None.. SOFA score, blood samples for plasma amino acids, procalcitonin and interleukin-6. Sepsis was determined to be the cause of encephalopathy in 14 of the 17 patients. Six patients developed septic shock, four died within the study period of 28 days. Within 12 h of the onset of septic encephalopathy, mean values of PCT and IL-6 were elevated ( p<0.001) and the amino acids unbalanced (the ratio of branched-chain to aromatic amino acids was decreased, p<0.001). During the course of sepsis the decreased amino acid ratio was significantly, but moderately, correlated with elevated PCT and IL-6 levels. On study days when PCT was higher than 2 ng/ml, the amino acid ratio was significantly lower. In no patient was severe liver dysfunction seen.. Metabolic disturbances with changes in amino acid levels can occur early in septic patients, without serious liver abnormalities. The present data suggest a possible role of amino acids in the pathogenesis of septic encephalopathy.

Topics: Amino Acids; Biomarkers; Brain Diseases, Metabolic; Calcitonin; Calcitonin Gene-Related Peptide; Case-Control Studies; Female; Humans; Inflammation; Intensive Care Units; Interleukin-6; Liver; Male; Middle Aged; Multiple Organ Failure; Prospective Studies; Protein Precursors; Sepsis

Predicting outcome in critical care remains difficult. One factor making the task difficult is, that the time elapsed between the onset of symptoms and admission to the intensive care unit is often unknown. The aim of this study is to evaluate the early course and predictive value of organ dysfunction monitored by Multiple Organ Dysfunction Score (MODS) and serum procalcitonin (PCT), microalbuminuria (M:Cr) following oesophageal tumor resection.. In our prospective study, 79 patients (67 survivors, 12 non-survivors) are involved all had elective oesophageal tumour resection. MODS was monitored daily (t1, t2, t3). Serum PCT levels were determined 24 hourly (t0, t24, t48, t72). M:Cr was measured before (tp), and after surgery (t0, t6, t24, t48, t72). For statistical analysis Wilcoxon rank sum test, Mann-Whitney U test, receiver operating characteristic curve analysis and logistic regression analysis were used.. Significantly higher MODS were observed in patients who died. As of organ dysfunction, PaO2/FiO2 ratio was below normal and remained significantly lower in non-survivors at t1, t2, t3. Serum PCT at t0 was normal in both groups. Levels at t24 increased significantly, and values were significantly higher in non-survivors. Levels remained elevated at t48 and t72 without statistically significant difference between the two groups. Preoperative M:Cr was normal. At t0 levels increased significantly, but then at t6-72 levels returned to normal without significant differences between survivors and non-survivors.. The PaO2/FiO2 ratio gave clear differentiation between survivors and non-survivors. It seems to be a sensitive measurement for predicting outcome following oesophagectomy. Routine measurement of serum PCT in the postoperative period may help predicting outcome but further studies are required.

Topics: Aged; Area Under Curve; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Esophagectomy; Female; Humans; Logistic Models; Male; Middle Aged; Multiple Organ Failure; Oxygen; Postoperative Period; Predictive Value of Tests; Prospective Studies; Protein Precursors; ROC Curve; Severity of Illness Index; Statistics, Nonparametric; Survival Analysis

Cardiopulmonary bypass is associated with an injury that may cause pathophysiological changes in the form of systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS). In the present study, we investigated the inflammatory response of patients with multiple organ dysfunctions following open-heart surgery. Plasma levels of cytokines (IL-1beta, IL-6, IL-8, IL-18) and procalcitonin (PCT) were measured on the first four postoperative days in 12 adult male patients with SIRS and two or more organ dysfunctions after myocardial revascularization (MODS group), and 15 patients without organ dysfunctions (SIRS group). All cytokines (except IL-1beta) and PCT were significantly elevated in MODS patients, with peak values at the first two postoperative days. The results of our study show a different expression of members of the IL-1 family following extracorporeal circulation. For the first time, we can document that IL-18 is involved in the inflammatory response and the initiation of the MODS following cardiopulmonary bypass. In addition to APACHE-II score, PCT, IL-8, and IL-18 may be used as parameters for the prognosis of patients with organ dysfunctions after cardiac surgery. Furthermore, it must be noted that the duration of the surgical procedure is one of the most important factors for the initiation of the inflammatory response.

Topics: Aged; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Cardiopulmonary Bypass; Cytokines; Humans; Interleukin-18; Male; Middle Aged; Multiple Organ Failure; Myocardial Revascularization; Postoperative Complications; Prognosis; Protein Precursors; Systemic Inflammatory Response Syndrome

Procalcitonin (PCT), interleukin-6 (IL-6), tumour necrosis factor a (TNFalpha), and interleukin-1beta (IL-1beta) are important clinical prognostic markers in ICU septic patients. The goal of the study was to determine whether continuous venovenous haemofiltration (CWH), using an AN69 haemofilte, leads to elimination of PCT, TNFalpha, IL-6 and IL-1beta in 13 septic patients with multi-organ failure. At the start of haemofiltration (0), 6 and 12 hours the mean afferent plasma concentration +/- SD of PCT (10.1 +/- 9.1, 7 +/- 6, 5.9 +/- 5.7 ng/ml), IL-6 (804.6 +/- 847.6, 611.7 +/- 528.4, 575.2 +/- 539.2 pg/ml), and that of TNFalpha (4.5 +/- 2.6, 4 +/- 3.1, 3.8 +/- 2.9 pg/ml) significantly declined during CVVH. The efferent plasma concentrations were significantly lower than the corresponding afferent concentrations. PCT; IL-6 and TNFalpha were detectable in the ultrafiltrate of all patients. IL-1beta was only detectable in the plasma of eight patients and the ultrafiltrate of five patients. The plasma clearance of PCT, IL-6 and TNFalpha significantly decreased after 12 hours as a result of a decline in the adsorptive elimination of the mediators due to progressive membrane saturation. We demonstrated that if PCT, IL-6 and TNFalpha are used as clinical prognostic markers in septic patients who are treated with CWIH using an AN69 membrane, one should be aware that their plasma level could be modified by the therapy. In addition CWH could represent an appropriate tool to remove a broad spectrum of proinflammatory mediators, if such removal is required in septic patients.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Cytokines; Female; Hemofiltration; Humans; Interleukin-1; Interleukin-6; Male; Middle Aged; Multiple Organ Failure; Probability; Prognosis; Prospective Studies; Protein Precursors; Sensitivity and Specificity; Sepsis; Survival Analysis; Tumor Necrosis Factor-alpha

To investigate whether marker(s) of systemic inflammation detect, at an early stage of acute pancreatitis, patients who may ultimately develop severe disease.. Prospective study.. University hospital emergency unit.. Thirty patients with mild acute pancreatitis (SEV0 group) and 27 with severe acute pancreatitis. Of the latter, 11 did not develop organ failure (SEV1 group), whereas the other 16 patients developed acute respiratory failure and 9 of them also developed renal failure (SEV2 group).. Blood samples were collected at admission to the hospital (T0), and at 12 hrs (T12) and 24 hrs (T24 after admission.. The plasma concentrations of procalcitonin (PCT), soluble E-selectin (sE-selectin), soluble interleukin-2 receptor (sIL-2R), and the serum concentration of C-reactive protein (CRP) were monitored. PCT levels at T0 were significantly higher in the SEV1 group (median 0.4 ng/mL, range 0.2-2.3) and the SEV2 group (0.8 ng/mL, 0.2-73.5) than in the SEV0 group (0.3 ng/mL, 0.1-3, p < .05 and p < .001, respectively). At T12, PCT level in the SEV2 group was significantly higher than that in the SEV1 group (2.2 ng/mL, 0.2-86.6 vs. 0.4 ng/mL, 0.3-2.8, p = .05), as it also was at T24 (2.2 ng/mL, 0.4-73.3 vs. 0.5 ng/mL, 0.3-4, p < .01). Among SEV2 patients, PCT concentration correlated negatively with the time elapsed between admission and the diagnosis of organ failure. At T12, sIL-2R levels of the SEV1 group (1,011 U/mL, range 334-2,211) and the SEV2 group (1,495 U/ml, range 514-4,526) both differed significantly from the SEV0 group (636 U/ml, range 356-1,678, p < .05 and p < .001, respectively) as they also did at T24. Although CRP level in the SEV1 group at T12 did not differ from the SEV0 group, the difference between SEV2 (272 microg/mL, range 46-462) and SEV0 was significant (53 microg/mL, range 5-243, p < 0.01). sE-selectin levels did not differ between groups.. At admission to hospital, concentrations of PCT, but not those of CRP, sE-selectin, or sIL-2R, are higher in patients with severe acute pancreatitis than in patients with mild pancreatitis. PCT test had sensitivity of 94% and specificity of 73% for development of organ failure. PCT may be useful to identify the patients who benefit from novel therapies aimed at modifying the course of systemic inflammation.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; E-Selectin; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Prognosis; Prospective Studies; Protein Precursors; Receptors, Interleukin-2; Sensitivity and Specificity; Severity of Illness Index; Statistics, Nonparametric; Time Factors

Sepsis is one of the most frequent causes of death after major burn injury. Usually, sepsis appears as a consequence of a gram-negative bacteriaemia with release of endotoxins. In this study, the plasma endotoxin levels of seven patients (three female, four male; average age 51.3 +/- 23.8 years) with burns between 43.5 and 78 % Total Body Surface Area (Abbreviated Burn Severity Index 8 - 12) were determined for five days after thermal trauma every three hours by ELISA and compared with the concentration of procalcitonin (PCT) and C-reactive protein (CRP). A calculation of the Horrowitz-Index (PaO(2)/FiO(2)) and the Pressure-Adjusted Heart Rate (HR x CVP/MAP) took place to show a possible correlation between the endotoxin concentration and the cardiopulmonary organ function. Additionally, we analysed whether operative treatment can influence the level of plasma endotoxin in the early phase after burn injury. At any time after burn trauma, endotoxins could be detected in the plasma of all patients. Between the second and third day, there was a considerable increase in the endotoxin concentration with a maximum after 57 hours of 0.48 +/- 0.32 EU/ml. Two patients with sepsis and death in the further course had a rather distinctive increase. From the fourth day on, occasional episodes of increases in endotoxin concentration were noted. Postoperatively, there was a short increase in plasma endotoxin on the second and fourth day. The plasma endotoxin level showed no correlation with the PCT and CRP or with the oxygenation in the patients' blood. However, a positive correlation could be observed with the Pressure-Adjusted Heart Rate (p = 0.0061; r(2) = 0.212). An explanation for the endotoxin increase after 57 hours could be the translocation of intestinal bacteria, the beginning of bacterial colonisation or decomposition products of the burn wound with protein-protein complexes. Later on, infectious diseases such as pneumonia with gram-negative bacteria are of importance, too. According to the Two-Hit Model, the increase of plasma endotoxin can serve as a trigger and cause a recurrence of systemic inflammation with the changes observed in cardiac organ function, multiple organ dysfunction, and multiple organ failure.

Topics: Adult; Aged; Aged, 80 and over; Burns; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Endotoxins; Female; Heart Rate; Humans; Male; Middle Aged; Multiple Organ Failure; Postoperative Complications; Predictive Value of Tests; Prognosis; Protein Precursors; Survival Rate; Systemic Inflammatory Response Syndrome

Because the use of procalcitonin (PCT) as a marker of bacterial infection has been advocated, this study was carried out to determine the usefulness of plasma PCT in the early diagnosis and differentiation of patients with non-infectious systemic inflammatory response syndrome (SIRS) from those with sepsis, and the relationship between plasma PCT level and severity of organ failure.. Thirty-five patients with non-septic SIRS (n = 16), sepsis (n = 7) or septic shock (n = 12) were included in this study. PCT and C-reactive protein (CRP) levels were measured and sepsis-related organ failure assessment (SOFA) score was calculated for these patients. Plasma PCT was measured by immunoluminometric assay.. The median (minimum, maximum) plasma PCT levels were 0.6 (0.1, 3.4) ng/mL in non-septic SIRS, 5.4 (0.9, 47.7) ng/mL in sepsis and 73.4 (9.6, 824.1) ng/mL in septic shock, and significant differences existed in plasma PCT levels among the three groups. The median (minimum, maximum) CRP levels were 13.8 (0.3, 48.8) mg/dL in non-septic SIRS, 23.3 (1.4, 26.6) mg/dL in sepsis and 17.4 (2.2, 34.1) mg/dL in septic shock, without significant differences among the three groups. A good correlation was found between plasma PCT level and SOFA score (rs = 0.766, P < 0.0001), although no correlation was found between CRP level and SOFA score.. CRP is increased by inflammatory disease as well as infection and is therefore not a good indicator of infection in patients with severe SIRS. On the other hand, PCT is a good indicator of severity of sepsis and organ failure in patients with severe SIRS since PCT levels correlated with sepsis and SOFA scores. PCT level is useful for diagnosis of sepsis and as an indicator of severity of organ failure in patients with SIRS.

Topics: Analysis of Variance; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycoproteins; Humans; Immunoassay; Male; Middle Aged; Multiple Organ Failure; Protein Precursors; Severity of Illness Index; Systemic Inflammatory Response Syndrome

Cardiopulmonary bypass (CPB) is associated with an immunological injury that may cause pathophysiological alterations in the form of a systemic inflammatory response syndrome (SIRS) or a multiple organ dysfunction syndrome (MODS). Previous studies on this issue have reported different changes of immunological parameters during and after CPB, but there are no reports about the lipopolysaccharide-binding protein (LBP) in relationship to other markers of inflammation in patients with MODS following cardiovascular surgery. In the present study, we investigated the acute-phase response of patients with MODS of infectious and non-infectious origin following open-heart-surgery. Plasma levels of procalcitonin (PCT), c-reactive protein (CRP), interleukin-6 (IL-6), and LBP were measured in the first four postoperative days in 12 adult male patients with the signs of SIRS and two or more organ dysfunctions after myocardial revascularization (MODS-group), and 12 patients without organ insufficiencies (SIRS-group). There were no significant differences regarding age, weight, height, preoperative NYHA-classification, preoperative LVEDP, or the number of anastomosis. Patients with MODS had a significantly longer operation time, duration of ischemia, and duration of extracorporeal circulation. None of the patients in the SIRS group died, whereas in the MODS group, 4 patients died due to septic multiorgan failure. Plasma PCT and IL-6 concentrations were significantly elevated in all MODS patients. CRP and LBP showed no differences between the MODS and the SIRS group. Comparing the MODS patients with and without positive microbial findings, we found significantly elevated levels of PCT and LBP in those patients with documented infections. Our results indicate that LBP may be a new marker for the differentiation between a severe non-infectious SIRS and an ongoing bacterial sepsis in the early postoperative course following CPB, while a microbiological result is still missing.

Topics: Acute-Phase Proteins; Acute-Phase Reaction; Aged; APACHE; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiopulmonary Bypass; Carrier Proteins; Humans; Interleukin-6; Length of Stay; Male; Membrane Glycoproteins; Middle Aged; Multiple Organ Failure; Myocardial Revascularization; Postoperative Complications; Protein Precursors; Systemic Inflammatory Response Syndrome

To compare procalcitonin (PCT) plasma levels of injured patients with the incidence and severity of systemic inflammatory response syndrome (SIRS), infection, and multiple organ dysfunction syndrome (MODS) and to assess the predictive value of PCT for these posttraumatic complications.. Retrospective study comparing patients with mechanical trauma in terms of severity of injury, development of infectious complications, and organ dysfunctions.. Level I trauma center with emergency room, intensive care unit, and research laboratory.. Four hundred five injured patients with an Injury Severity Score of > or =9 points were enrolled in this study from January 1994 to February 1996.. Blood samples were collected on the day of admission and on days 1, 3, 5, 7, 10, 14, and 21 thereafter.. We determined PCT serum levels using a specific immunoluminometric assay. We retrospectively evaluated the occurrence of SIRS, sepsis, and MODS using patients' charts. Mechanical trauma led to increased PCT plasma levels dependent on the severity of injury, with peak values on days 1 and 3 (p < .05) and a continuous decrease within 21 days after trauma. Patients who developed SIRS demonstrated a significant (p < .05) increase of peak PCT plasma levels compared with patients without SIRS. The highest PCT plasma concentrations early after injury were observed in patients with sepsis (6.9+/-2.5 ng/mL; day 1) or severe MODS (5.7+/-2.2 ng/mL; day 1) with a sustained increase (p < .05) for 14 days compared with patients with an uneventful posttraumatic course (1.1+/-0.2 ng/mL). Moreover, these increased PCT plasma levels during the first 3 days after trauma predicted (p < .0001; logistic regression analysis) severe SIRS, sepsis, and MODS.. These data indicate that PCT represents a sensitive and predictive indicator of sepsis and severe MODS in injured patients. Routine analysis of PCT levels seems to aid early recognition of these posttraumatic complications. Thus, PCT may represent a useful marker to monitor the inflammatory status of injured patients at risk.

Topics: Adult; APACHE; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycoproteins; Humans; Logistic Models; Male; Multiple Organ Failure; Predictive Value of Tests; Protein Precursors; Retrospective Studies; Sepsis; Severity of Illness Index; Statistics, Nonparametric; Time Factors; Wounds and Injuries

Sexual hormones are potent regulators of various immune functions. Although androgens are immunosuppressive, estrogens protect against septic challenges in animal models. This study correlates sexual dimorphism with the incidence of posttraumatic complications in severely injured patients.. From January of 1991 to February of 1996, 1,276 consecutive injured patients (Injury Severity Score [ISS] > or = 9 points) were studied. Males (n = 911) did not differ from females (n = 365) with regard to severity of injury (ISS) and injury pattern.. The incidence of posttraumatic sepsis (30.7%) and multiple organ dysfunction syndrome (29.6%) was significantly increased in severely injured males with ISS > or = 25 points in comparison to the equivalent group of females (sepsis, 17.0%; multiple organ dysfunction syndrome, 16.0%). No difference was found in patients with ISS < 25 points. Moreover, plasma levels of procalcitonin and interleukin-6 were elevated (p < 0.05) in severely injured males compared with females.. Sex influences posttraumatic morbidity in severely injured patients and supports the concept that females are immunologically better positioned toward a septic challenge.

Topics: Adult; Biomarkers; Calcitonin; Calcitonin Gene-Related Peptide; Female; Humans; Incidence; Injury Severity Score; Interleukin-6; Male; Morbidity; Multiple Organ Failure; Multiple Trauma; Prospective Studies; Protein Precursors; Retrospective Studies; Sepsis; Sex Characteristics; Sex Distribution; Survival Analysis

Procalcitonin (PCT), a marker of bacterial sepsis, may also act as a mediator of the inflammatory response to infection, and thus influence outcome.. To investigate the relationship between PCT, interleukin (IL)-10, tumor necrosis factor (TNF), organ failure, and mortality in pediatric septic shock.. Prospective observational study.. A 16-bed pediatric intensive care unit of a university hospital.. A total of 75 children with septic shock having a median age of 43.1 months (range, 0.1-192 months). Children who had received antibiotics for >24 hrs were excluded. A total of 37 patients (49%) had meningococcal disease, and 72 patients (96%) required mechanical ventilation.. The pediatric risk of mortality (PRISM) score, multiple organ system failure (MOSF) score, duration of ventilation, length of ICU stay, and outcome were recorded. PCT, IL-10, and TNF were measured at admission to the intensive care unit. Sequential PCT levels were available at 0 hrs and 24 hrs in 39 patients (52%).. Observed mortality was 21/75 (28%). Data are median (range). The admission PCT (p = .0002) and TNF levels (p = .0001) were higher in children with higher MOSF scores. In survivors and nonsurvivors, the admission PCT was 82 ng/mL vs. 273 ng/mL (p = .03), IL-10 was 62 pg/mL vs. 534 pg/mL (p = .03), and TNF was 76 pg/mL vs. 480 pg/mL (p = .001), respectively. Area under the mortality receiver operating characteristic curve was 0.73 for PCT, 0.67 for IL-10, and 0.76 for TNF, compared with 0.83 for the PRISM score. Of 39 children, 16 (41%) with sequential PCT measurements showed no fall in PCT after 24 hrs treatment. These children had higher admission levels of IL-10 (p = .03), and TNF (p = .03) compared with children who demonstrated a subsequent fall in PCT. Although the former did not have a higher median PRISM (p = .28) or MOSF score (p = .19), observed mortality was 44% (7 of 16) compared with 9% (2 of 23) (p = .02).. The admission PCT, like TNF and IL-10, is related to the severity of organ failure and mortality in children with septic shock. A fall in PCT after 24 hrs of treatment may have favorable prognostic significance.

Topics: Adolescent; Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Humans; Infant; Intensive Care Units, Pediatric; Interleukin-10; Length of Stay; Multiple Organ Failure; Prognosis; Prospective Studies; Protein Precursors; Respiration, Artificial; ROC Curve; Severity of Illness Index; Shock, Septic; Tumor Necrosis Factor-alpha

The elimination of procalcitonin and the course of plasma concentrations during continuous veno-venous haemodiafiltration were measured in patients with sepsis or multiple organ dysfunction syndrome, because these patients are a main target group for the measurement of procalcitonin and often require renal replacement therapy. Procalcitonin was measured in the prefilter plasma and the filtrate at 5 min, 15 min and 1, 2, 4, 6, 12, 24 h after set-up of continuous veno-venous haemodiafiltration. In a prospective study, 19 patients with plasma levels of procalcitonin > 3 ng mL-1 and acute oliguric renal failure treated with continuous veno-venous haemodiafiltration using a polysulphone membrane, were evaluated for the study of clearance. Twenty-one control patients (procalcitonin < 2 ng mL-1) were studied to determine whether filtration itself induced a procalcitonin response. No interventions were required. In patients with low procalcitonin concentrations (procalcitonin < 2 ng mL-1) continuous veno-venous haemodiafiltration did not cause a rise in procalcitonin. In patients with increased procalcitonin plasma concentrations (> 3 ng mL-1), the protein was removed through the polysulphone membrane, with a final clearance of 4 mL min-1 after the initial adsorption period (clearance 0.4-0.9 mL min-1 during the first hour of continuous veno-venous haemodiafiltration). Thus, on the average, approximately 10% of plasma concentrations were measurable in the filtrate ultimately. However, procalcitonin plasma levels were not significantly altered during continuous veno-venous haemodiafiltration (86% of the initial concentration after 24 h). Although procalcitonin is removed from the plasma during continuous veno-venous haemodiafiltration in measurable amounts plasma procalcitonin concentrations did not change significantly during haemodiafiltration. Procalcitonin thus can also be used as a diagnostic parameter in patients undergoing continuous veno-venous haemodiafiltration.

Topics: Acute Kidney Injury; Adsorption; Aged; Biocompatible Materials; Calcitonin; Calcitonin Gene-Related Peptide; Female; Follow-Up Studies; Glycoproteins; Hemodiafiltration; Humans; Male; Membranes, Artificial; Middle Aged; Multiple Organ Failure; Polymers; Prospective Studies; Protein Precursors; Renal Replacement Therapy; Sepsis; Shock, Septic; Statistics, Nonparametric; Sulfones

Procalcitonin (PCT) was shown to be related to the severity of bacterial infection and is recommended as a new parameter of inflammation and infection. To evaluate the prognostic value in septic shock, PCT levels were repeatedly determined and compared with tumour necrosis factor-alpha (TNF-alpha)- and interleukin (IL)-6 bioactivity as well as with C-reactive protein (CRP) serum levels.. Twenty-four surgical patients with septic shock were included. Eight patients died within the study period of 14 days.. Serum levels of TNF-(WEHI 164) and IL-6 (B13-29 subclone 9) bioactivity, CRP and PCT were determined on days 1, 3, 5, 7, 10 and 14 following diagnosis of septic shock.. Survivors and non-survivors were comparable in terms of age and severity of sepsis characterized by the APACHE II score and multiple-organ-failure score. Predominant causes of sepsis were peritonitis and necrotiszing pancreatitis. TNF levels increased in non-survivors with no significant difference to survivors. IL-6 bioactivity was increased on day 1 (P = 0.06) and remained elevated in non-survivors, in whom it was significant on day 7 (P<0.05). CRP was constantly elevated with no difference between the groups. In nonsurvivors PCT remained increased, while the course of survivors was characterized by decreased values which were significantly lower (P<0.05) at every time point compared with those patients who died. A significant correlation could be found on day 1 (P<0.05) and at the end of the observation period (P<0.01) when comparing PCT levels with the multiple-organ-failure score.. PCT seems to be a more reliable prognostic parameter in septic shock than IL-6, while TNF and CRP did not show any difference between survivors and non-survivors. These data indicate that PCT may represent a valuable parameter not only in the diagnosis of sepsis but also in the clinical course of the disease.

Topics: APACHE; Biomarkers; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Glycoproteins; Humans; Interleukin-6; Male; Middle Aged; Multiple Organ Failure; Pancreatitis; Peritonitis; Prognosis; Protein Precursors; Severity of Illness Index; Shock, Septic; Tumor Necrosis Factor-alpha

To evaluate the Procalcitonin (PCT) clearance during continuous veno-venous hemodiafiltration (CVVHD).. Case report. ++ Surgical intensive care unit.. 51-year-old man, who had undergone total thyroidectomy about ten years before owing to multiple endocrine neoplasia 2 (MEN 2), suffering from multiple organ dysfunction syndrome (MODS) with acute renal failure after severe trauma caused by a traffic accident.. The samplings of prefilter (afferent) and post-filter (efferent) blood and of ultradiafiltrate were 6 times performed during 24 h of CVVHD to calculate the PCT clearance of hemdiafiltration. During the first half period of CVVHD the serum PCT concentration did not decrease, though PCT had been eliminated from serum. On the other hand during the latter half period of it the serum PCT value decreased (from 46.8 ng/ml to 29.4 ng/ml) and the amount of the eliminated PCT from serum was about 100 ng per minute and its clearance was 2.3 approximately 3.4 ml/min.. The CVVHD could eliminate PCT from serum. First it was brought about by the adsorption by the filter membrane and then by ultradiafiltration.

Topics: Acute Kidney Injury; Calcitonin; Calcitonin Gene-Related Peptide; Hemodiafiltration; Humans; Male; Metabolic Clearance Rate; Middle Aged; Multiple Endocrine Neoplasia Type 2a; Multiple Organ Failure; Multiple Trauma; Protein Precursors

Monitoring the immune responses in critically ill patients helps us to understand pathophysiological aspects of inflammation, immune deficiency, and infection, and to assess objective measures of therapeutic success. Monitoring should be adapted to the individual therapeutic approach. We recommend the measurement of substances in plasma that indicate systemic inflammatory processes, such as tumour necrosis factor (TNF), interleukin (IL)-6, and C-reactive protein (CRP), and invasive infection or endotoxaemia, such as procalcitonin (PCT). Moreover, it is important to evaluate the functional activity of the immune system, which can fail like other organs in the process of multiple organ failure. The resulting immunodeficiency results in failure to eliminate invading pathogens. Plasma concentration of IL-10 and of monocytic function and phenotype (HLA-DR+, CD14+ monocytes, ex vivo TNF secretion capacity) are the most valuable measurements for this purpose.

Topics: C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Cardiac Surgical Procedures; Critical Illness; Endotoxemia; Glycoproteins; HLA-DR Antigens; Humans; Immunoglobulin A; Immunoglobulin M; Immunoglobulins, Intravenous; Immunologic Deficiency Syndromes; Interleukin-10; Interleukin-6; Lipopolysaccharide Receptors; Mediastinitis; Monitoring, Immunologic; Monocytes; Multiple Organ Failure; Protein Precursors; Surgical Wound Infection; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha