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PubMed2004

Evaluation of natural killer cells as diagnostic markers of early onset neonatal sepsis: comparison with C-reactive protein and interleukin-8.

This study was conducted on thirty-seven neonates and healthy neonates (sixteen full term and fourteen preterm). The study aimed at revealing the role played by the NK cells in neonatal sepsis and evaluating the sensitivity of NK cell number and cytotoxicity as diagnostic markers in infants with suspected early neonatal sepsis compared with the circulating cytokine IL-8 and CRP levels. All samples of peripheral blood lymphocytes were subjected to determination of CD16 and CD56 positive cells using flow cytometry and NK cytotoxicity using the standard 4h 51Cr release assay. Sera were separated to measure IL-8 using ELISA. Determination of CRP, using turbdimetric assay, as well as blood cultures were done for patient's group only. Out of the 37 cases of suspected early neonatal sepsis, 16 were given final diagnosis of sepsis. Seven infants (43.8%) in the sepsis group had culture-proven diagnosis, one of which had meningitis. The median CRP value was significantly higher in sepsis group (88 mg/L; range: 17-159 mg/L) compared with that in non-septic group (15.4 mg/L; range: 7.6-23.2 mg/L, p < 0.001) only 12-60 h after admission. On the other hand, newborns in the sepsis group had significantly higher serum levels of IL-8 (median 310 pg/mL; range: 37-583 pg/ml) at study entry than that in the non septic group (median 63 pg/mL; range: 32-94 pg/ml, P < 0.001). On admission, the NK activity, rather than the number of CD16 and CD56 positive cells was much affected where NK cytotoxicity was significantly lower in sepsis group (3.4 +/- 2.1%, range 0.9-7%) than that of the nonseptic group (18.3 +/- 6.7%: range 10.7- 25.3%, p < 0.01) and healthy neonates (23.8 +/- 4.7%: range 12.2-32.3%, p < 0.001). We may conclude that defective NK cell activity rather than NK cell number plays an important role in susceptibility to early onset neonatal sepsis. Evaluation of NK cytotoxicity as a marker in early diagnosis of neonatal sepsis reveals that the sensitivity, specificity and predictive values of reduced NK cytotoxicity (10% killing) was higher than both of CRP and IL-8, either individually or in combination. Additionally, reduced NK cytotoxicity showed high correlation with the severity and outcome of neonatal sepsis. Our data raise the possibility that the addition of NK cell activity to the standard work-up of critically ill patients with suspected sepsis could increase diagnostic certainty and generate an improved patient management.

Bacteremia↗
PubMed1990

Long peritoneal lavage decreases pancreatic sepsis in acute pancreatitis.

Late infection of devitalized pancreatic and peripancreatic tissue has become the major cause of morbidity in severe acute pancreatitis. Previous experience found that peritoneal lavage for periods of 48 to 96 hours may reduce early systemic complications but did not decrease late pancreatic sepsis. A fortunate observation led to the present study of the influence of a longer period of lavage on late sepsis. Twenty-nine patients receiving primary nonoperative treatment for severe acute pancreatitis (three or more positive prognostic signs) were randomly assigned to short peritoneal lavage (SPL) for 2 days (15 patients) or to long peritoneal lavage (LPL) for 7 days (14 patients). Positive prognostic signs averaged 5 in both groups but the frequency of five or more signs was higher in LPL (71%) than in SPL (47%). Eleven patients in each group had early computed tomographic (CT) scans. Peripancreatic fluid collections were shown more commonly in LPL (82%) than in SPL (54%) patients. Longer lavage dramatically reduced the frequency of both pancreatic sepsis (22% LPL versus 40% SPL) and death from sepsis (0% LPL versus 20% SPL). Among patients with fluid collections on early CT scan, LPL led to a more marked reduction in both pancreatic sepsis (33% LPL versus 83% SPL) and death from sepsis (0% LPL versus 33% SPL). The differences were even more striking among 17 patients with five or more positive prognostic signs. In this group the incidence of pancreatic sepsis was 30% LPL versus 57% SPL and of death from sepsis 0% (LPL) versus 43% (SPL) (p = 0.05). In these patients, overall mortality was also reduced (20% LPL versus 43% SPL). When 20 patients treated by LPL were compared with 91 other patients with three or more positive prognostic signs who were treated without lavage or by lavage for periods of 2 to 4 days, the frequency of death from pancreatic sepsis was reduced from 13% to 5%. In those with five or more signs, the incidence of sepsis was reduced from 40% to 27% (p = 0.03) and of death for sepsis from 30% to 7% (p = 0.08). These findings indicate that lavage of the peritoneal cavity for 7 days may significantly reduce both the frequency and mortality rate of pancreatic sepsis in severe acute pancreatitis.

Abscess↗
PubMed1994

Skeletal muscle partial pressure of oxygen in patients with sepsis.

OBJECTIVE: In order to obtain direct evidence for tissue hypoxia in patients with sepsis oxygen, partial pressure was measured within skeletal muscle. Furthermore, serial intermittent and continuous measurements of skeletal muscle PO2 in patients with sepsis were used to find out whether skeletal muscle oxygenation may change in the course of sepsis and depends on the severity of sepsis. DESIGN: Prospective study. SETTING: Intensive care unit of a university hospital. PATIENTS: Intensive care patients (n = 98) with sepsis (group 1, n = 39; group 4, n = 28), limited infection (group 2, n = 16), and cardiogenic shock (group 3, n = 15). INTERVENTIONS: Pulmonary artery catheterization; standard antibiotic therapy and volume replacement. MEASUREMENTS AND MAIN RESULTS: Skeletal muscle PO2 was determined by polarographic needle electrodes or catheter probes. In patients with sepsis (n = 67), no evidence for skeletal muscle hypoxia was obtained from the PO2 distribution within biceps muscle. Mean skeletal muscle PO2 was increased in patients with sepsis (group 1, 48 torr [6.4 kPa]) compared with patients with limited infection (group 2, 28 torr [3.7 kPa]), p < .001) and with patients with cardiogenic shock (group 3, 22 torr [2.9 kPa], p < .001). Serial measurements of the PO2 distribution during seven consecutive days in another 28 patients (group 4) with sepsis showed that a more severe degree of sepsis was associated with an increase of mean skeletal muscle (p < .001). These results were confirmed by continuous measurements of mean skeletal muscle PO2, using PO2 catheters. CONCLUSIONS: In patients with sepsis, oxygen transport to skeletal muscle was not critically reduced. Serial intermittent and continuous measurements of skeletal muscle PO2 showed that skeletal muscle PO2 increased in relation to the severity of the stage of sepsis. Our findings suggest that oxygen utilization within skeletal muscle decreased with deterioration of sepsis, thereby increasing skeletal muscle PO2.

Adult↗
PubMed1996

Bedside prediction of mortality from bacteremic sepsis. A dynamic analysis of ICU patients.

The prognosis in patients with sepsis depends on severity of acute illness, underlying chronic diseases, and complications associated with infection. Adjusting for these factors is essential for evaluation of new therapies. The purpose of the present study was to determine variables readily identifiable at the bedside that predict mortality in intensive care unit (ICU) patients with sepsis and positive blood cultures. For a 5-yr period, all patients of a surgical ICU presenting with positive blood cultures and sepsis were systematically analyzed for clinical variables and organ dysfunctions at the day of onset of sepsis and bacteremia and during the subsequent clinical course. The prognostic value of these variables was determined using logistic regression procedures. Of the 5,457 admissions to the ICU, 176 patients developed sepsis with positive blood cultures (3.2 per 100 admissions). The fatality rate was 35% at 28 days after the onset of sepsis; in-hospital mortality was 43%. Independent predictors of mortality at onset of sepsis were previous antibiotic therapy (odds ratio [OR], 2.40; 95% confidence interval [CI95], 1.59 to 3.62; p = 0.034), hypothermia (OR, 1.43; CI95, 1.04 to 2.44; p = 0.030), requirement for mechanical ventilation (OR, 2.97; CI95, 1.96 to 4.51; p = 0.009), and onset-of-sepsis APACHE II score (OR, 1.21; CI95, 1.13 to 1.29; p < 0.001). Vital organ dysfunctions developing after the onset of sepsis influenced outcome markedly. The best two independent prognostic factors were the APACHE II score at the onset of sepsis (OR, 1.13 per unit; CI95, 1.08 to 1.17; p = 0.0016) and the number of organ dysfunctions developing thereafter (OR, 2.39; CI95, 2.02 to 2.82; p < 0.001). In ICU patients with sepsis and positive blood cultures, outcome can be predicted by the severity of illness at onset of sepsis and the number of vital organ dysfunctions developing subsequently. These variables are easily assessed at the bedside and should be included in the evaluation of new therapeutic strategies.

APACHE↗
PubMed2004

Serum levels of the apoptosis-associated molecules, tumor necrosis factor-alpha/tumor necrosis factor type-I receptor and Fas/FasL, in sepsis.

STUDY OBJECTIVE: s: Numerous reports suggest that apoptosis may play an important role in the sepsis syndrome. The objective of the present study was to examine the levels of molecules associated with apoptosis belonging to the tumor necrosis factor (TNF)-alpha/TNF type-I receptor (TNFRI) and Fas ligand (FasL)/Fas receptor (Fas) pathways in patients with sepsis. PATIENTS AND METHODS: Twenty-two patients with sepsis (14 patients with severe sepsis and 8 patients with sepsis), and 6 healthy volunteers were evaluated. Sequential analysis of the serum levels of TNF-alpha, TNFRI, FasL, and Fas were performed in these patients using enzyme-linked immunosorbent assays. RESULTS: Detectable levels of TNF-alpha were found in only 8 of 14 patients with severe sepsis. Patients with severe sepsis and sepsis had similarly increased levels of FasL, compared with healthy individuals (p < 0.05). Higher levels of TNFRI and Fas were found in patients with severe sepsis than in patients with sepsis and healthy volunteers (p < 0.001 and p < 0.01, respectively). Fas levels were also higher in patients who died than in those who survived (p < 0.01). A direct relationship was found between serum levels of TNFRI and Fas, and multiorgan dysfunction (sequential organ failure assessment score) [p < 0.0001]. CONCLUSIONS: These results suggest that the TNF-alpha/TNFRI and FasL/Fas systems may be involved in the pathogenesis of sepsis. Serum levels of the death-receptors, TNFRI and Fas, could serve as potential markers of the severity of human sepsis.

Adult↗
PubMed1991

Fibrinolysis and coagulation in patients with infectious disease and sepsis.

Sepsis is often associated with hemostatic dysfunction. This study aimed to relate changes in fibrinolysis and coagulation parameters to sepsis and sepsis outcome. Urokinase-type plasminogen activator (u-PA) antigen, tissue-type plasminogen activator (t-PA) antigen and activity, plasminogen activator inhibitor (PAI) type 1 antigen, PAI activity, antithrombin (AT) III activity, and protein C activity were measured in 24 patients suffering from sepsis or septic shock and the results were compared with those observed in 30 non-sepsis patients with severe infectious disease. The u-PA level was markedly increased in plasma of sepsis patients as compared to non-sepsis patients (11.5 +/- 9.4 versus 1.6 +/- 1.5 ng/ml, p less than 0.0001). PAI-1 antigen and t-PA activity showed a significant increase in sepsis patients (320 +/- 390 ng/ml versus 120 +/- 200 ng/ml, and 3.0 +/- 3.6 IU/ml versus 1.0 +/- 0.7 IU/ml, respectively, p less than 0.01). AT III was decreased in sepsis patients (58 +/- 28% in sepsis versus 79 +/- 26% in severe infectious disease, p less than 0.01) as was protein C (30 +/- 18% versus 58 +/- 27%, p less than 0.001). No significant difference was found for t-PA antigen nor for PAI activity. Nonsurvivors of sepsis were distinguished mainly by a high u-PA antigen level and increased t-PA activity. It is concluded that plasma u-PA antigen showed the strongest significant difference, among the parameters evaluated, between sepsis and severe infection. u-PA antigen may be of prognostic value in patients admitted to the medical intensive care unit for severe infectious disease.

Adult↗
PubMed2000

Vancomycin for prophylaxis against sepsis in preterm neonates.

BACKGROUND: Nosocomial, late onset sepsis occurs in up to 50% of infants of less than 1000gm at birth. The commonest organism isolated is coagulase negative staphylococcus (CoNS). A number of studies have evaluated the efficacy or prophylactic low dose vancomycin given either as a continuous infusion added to the infant's hyperalimentation fluid or by intermittent intravenous administration and these studies in very low birth weight infants are the subject of this review. OBJECTIVES: To evaluate the safety and efficacy of vancomycin prophylaxis for the prevention of late-onset sepsis, coagulase negative staphylococcal sepsis, mortality, and effects on length of stay, total vancomycin exposure, evidence of vancomycin toxicity, and the development of vancomycin resistant organisms in the preterm neonate. SEARCH STRATEGY: Searches were made of Medline, (MeSH terms: Vancomycin and Sepsis; limits: age groups, newborn infants), HealthStar and EMBase, electronic abstracts, personal files and conference proceedings. SELECTION CRITERIA: Randomized controlled trials which compared the incidence of sepsis and mortality in preterm neonates receiving vancomycin prophylaxis versus a control group receiving no prophylaxis. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including the overall incidence of sepsis, the incidence of coagulase negative staphylococcal sepsis, mortality, length of stay, total vancomycin exposure, evidence of vancomycin toxicity, and the development of vancomycin resistant organisms were excerpted from previous clinical trials. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: The administration of prophylactic vancomycin reduced the incidence of both total neonatal nosocomial sepsis and coagulase negative staphylococcal sepsis in eligible preterm infants. Mortality, length of stay, and evidence of vancomycin toxicity were not significantly different between the two groups. There was insufficient evidence to ascertain the risks of development of vancomycin resistant organisms in the nurseries involved in these trials. REVIEWER'S CONCLUSIONS: The use of prophylactic vancomycin in low doses reduces the incidence of nosocomial sepsis in the neonate. The methodologies of these studies may have contributed to the low rate of sepsis in the treated groups, as the blood cultures drawn from central lines may have failed to grow due to the low levels of vancomycin in the infusate. Although there is a theoretical concern regarding the development of resistant organisms with the administration of prophylactic antibiotic, there is insufficient evidence to ascertain the risks of development of vancomycin resistant organisms. Few clinically important benefits have been demonstrated for very low birth weight infants treated with prophylactic vancomycin. It therefore appears that routine prophylaxis with vancomycin should not be undertaken at present.

Anti-Bacterial Agents↗
PubMed1997

Differential activation of protein kinase A in various regions of myocardium during sepsis.

Changes in the activities of protein kinase A (PKA) (cAMP-dependent protein kinase) in various regions of rat myocardium during different cardiodynamic phases of sepsis were studied in an attempt to understand the pathophysiology of cardiac dysfunction during sepsis. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 hr, respectively, after CLP. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two types of PKA, Type I (eluted at low ionic strength) and Type II (eluted at high ionic strength), were collected, and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. Under physiological conditions, Type I PKA activities were unevenly distributed (left atrium > right atrium > pacemaker region > left ventricle > right ventricle > ventricular septum) while Type II PKA activities were evenly distributed among different regions of myocardium. During early sepsis, Type I PKA activities remained unchanged while Type II PKA activities were activated by 32 and 70% in right atrium and pacemaker regions, respectively. During late sepsis, Type I PKA activities were stimulated by 228% in ventricular septum while Type II PKA activities were not affected. These data demonstrate that different PKA activities exist in various regions of the myocardium and that PKA activities were preferentially activated in certain areas during the progression of sepsis. Since PKA plays an important role in the regulation of myocardial function and metabolism, the activation of PKA in different regions of myocardial during different stages of sepsis may contribute to the altered cardiac function during the progression of sepsis.

Animals↗
PubMed2001

Comparison of procalcitonin with C-reactive protein and serum amyloid for the early diagnosis of bacterial sepsis in critically ill neonates and children.

OBJECTIVES: To evaluate procalcitonin (PCT) as a diagnostic marker of bacterial sepsis in critically ill neonates and children and to compare the results of PCT with those of C-reactive protein (CRP) and serum amyloid (SAA). DESIGN AND SETTING: Prospective, observational study in neonatal and pediatric intensive care units. PATIENTS: A total of 116 divided into four groups according to age and diagnosis: neonates (aged 3-30 days) with sepsis (n = 20), neonates without sepsis (n = 26), children (aged 2-12 years) with sepsis (n = 32), and children without sepsis (n = 38). INTERVENTIONS: Serum PCT, CRP, and SAA were measured on admission or when a bacterial sepsis was suspected. Area under the receiver operating characteristic (ROC) curve, optimum predictive values, and optimum diagnostic cut off values were evaluated. RESULTS: Admission PCT was significantly higher in neonates and children with sepsis than in the other groups. In the neonates the area under the ROC curve was 0.99 for PCT, 0.95 for CRP, and 0.98 for SAA; in the children it was 1 for PCT, 0.93 for CRP, and 0.96 for SAA. Cutoff concentrations for optimum prediction of sepsis in the neonates were PCT > 6.1 ng/ml (diagnostic efficiency: 93.8%), CRP > 23.0 mg/l (89.7%), and SAA > 41.3 mg/l (95.3%); in the children they were PCT > 8.1 ng/ml (100%), CRP > 22.1 mg/l (89.8%), and SAA > 67.2 mg/l (94.4%). CONCLUSION: In critically ill children PCT concentration is a better diagnostic marker of sepsis than CRP and SAA. In critically ill neonates, however, PCT, CRP, and SAA are similar diagnostic markers of sepsis. A PCT concentration higher than 8.1 ng/ml identified all children with bacterial sepsis.

Amyloid↗
PubMed2006

The association of sepsis syndrome and organ dysfunction with mortality in emergency department patients with suspected infection.

STUDY OBJECTIVE: The critical care community has used standard criteria for defining the sepsis syndromes and organ dysfunction for more than 15 years; however, these criteria are not well validated in the emergency department (ED) setting. The study objectives in our ED population of patients admitted to the hospital are to determine the prevalence of the sepsis syndromes, quantify inhospital mortality and 1-year survival associated with the sepsis syndromes, and assess the inhospital and 1-year survival associated with organ dysfunctions. METHODS: This was a prospective, observational, cohort study from February 1, 2000, to February 1, 2001 in an urban university hospital ED with 50,000 annual visits. There were 3,102 (96% of eligible) consecutive adult patients (aged 18 years or older) with suspected infection (as indicated by the clinical decision to obtain a blood culture) who were enrolled. Patients were screened for systemic inflammatory response syndrome (SIRS) (2 or more indicators of inflammatory response), sepsis (SIRS plus suspected infection), severe sepsis (sepsis plus organ dysfunction), septic shock (sepsis plus hypotension refractory to an initial fluid challenge), and number of organs with acute dysfunction. Main outcome measure was inhospital and 1-year mortality. RESULTS: Overall inhospital mortality was 4.1% and 1-year mortality was 22%. The inhospital mortality rates were suspected infection without SIRS 2.1%, sepsis 1.3%, severe sepsis 9.2%, and septic shock 28%. Compared to suspected infection without SIRS, adjusted risks of inhospital mortality were severe sepsis (odds ratio [OR] 4.0; 95% confidence interval [CI] 2.6 to 6.3) and septic shock (OR 13.8; 95% CI 6.6 to 29). Severe sepsis (OR 2.2; 95% CI 1.8 to 2.6) and septic shock (OR 3.5; 95% CI 2.3 to 5.3) also predicted 1-year mortality. The presence of SIRS criteria alone had no prognostic value for either endpoint. Each additional organ dysfunction increased the adjusted 1-year mortality hazard by 82% (pulse rate: 1.82, 95% CI 1.7 to 2.0). CONCLUSION: Immediate identification of acute organ dysfunction in ED patients with suspected infection may help select patients at increased short- and long-term mortality risk. SIRS criteria offered no additional prognostic value, whereas each additional organ dysfunction increased the 1-year mortality risk.

Adult↗
PubMed2005

Oxytocin protects against sepsis-induced multiple organ damage: role of neutrophils.

BACKGROUND: Sepsis, commonly associated with enhanced generation of reactive oxygen metabolites, leads to multiple organ dysfunctions. The neurohypophyseal hormone oxytocin (OT), released during social contact, was recently shown to modulate the immune and inflammatory processes. We investigated the protective role of OT against sepsis-induced pelvic inflammation. MATERIALS AND METHODS: Under anesthesia, sepsis was induced in female Sprague-Dawley rats (200-250 g) by cecal ligation and perforation method. Sham-operated rats served as controls. Either saline or OT (1 mg/kg) was given subcutaneously immediately after and at the 16th hour, and rats were decapitated at the 24th hour of sepsis induction. Colon, uterus, and liver samples were obtained for the histopathological analysis of damage and for the measurement of myeloperoxidase (MPO) activity, indicating neutrophil infiltration, malondialdehyde (MDA), indicating lipid peroxidation, and glutathione (GSH), a key antioxidant, levels. RESULTS: Colonic, uterine and liver MDA levels in the sepsis group were significantly increased (P < 0.01-P < 0.001), while colonic and uterine GSH levels were decreased (P < 0.05-P < 0.01) when compared to the control group. OT treatment reversed the MDA and GSH levels back to the control levels, while hepatic GSH levels were not altered. MPO activity in the colon and liver was increased by sepsis (P < 0.05-P < 0.001) while OT treatment abolished the elevated MPO activity. Collagen levels in the uterus and liver were increased by sepsis (P < 0.01) and OT treatment reduced the collagen levels in both tissues (P < 0.01-P < 0.05). Serum TNF-alpha levels were significantly increased by sepsis (P < 0.001) and OT treatment abolished the sepsis-induced increase in TNF-alpha levels. CONCLUSIONS: OT protects against sepsis-induced oxidative damage by acting as an antioxidant agent and its protective effect in the colon and liver appears to be dependent on its inhibitory effect on neutrophil infiltration. Our results suggest that OT may have a therapeutic value in limiting sepsis-associated multiple organ damage.

Animals↗
PubMed1996

Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network.

OBJECTIVE: Late-onset sepsis (occurring after 3 days of age) is an important problem in very low birth weight (VLBW) infants. To determine the current incidence of late-onset sepsis, risk factors for disease, and the impact of late-onset sepsis on subsequent hospital course, we evaluated a cohort of 7861 VLBW (401 to 1500 gm) neonates admitted to the 12 National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers during a 32-month period (1991 to 1993). METHODS: The NICHD Neonatal Research Network maintains a prospectively collected registry of all VLBW neonates cared for at participating centers. Data from this registry were analyzed retrospectively. RESULTS: Of 6911 infants who survived beyond 3 days, 1696 (25%) had one or more episodes of blood culture-proven sepsis. The vast majority of infection (73%) were caused by gram-positive organisms, with coagulase-negative staphylococci accounting for 55% of all infections. Rate of infection was inversely related to birth weight and gestational age. Complications of prematurity associated with an increased rate of infection included intubation, respiratory distress syndrome, prolonged ventilation, bronchopulmonary dysplasia, patent ductus arteriosus, severe intraventricular hemorrhage, and necrotizing enterocolitis. Among infants with bronchopulmonary dysplasia, those with late-onset sepsis had a significantly longer duration of mechanical ventilation (45 vs 33 days; p <0.01). Late-onset sepsis prolonged hospital stay: the mean number of days in the hospital for VLBW neonates with and without late-onset sepsis was 86 and 61 days, respectively (p <0.001). Even after adjustment for other complications of prematurity, including intraventricular hemorrhage, necrotizing enterocolitis, and bronchopulmonary dysplasia, infants with late-onset sepsis had a significantly longer hospitalization (p <0.001). Moreover, neonates in whom late-onset sepsis developed were significantly more likely to die than those who were uninfected (17% vs 7%; p <0.000 1), especially if they were infected with gram-negative organisms (40%) or fungi (28%). Deaths attributed to infection increased with increasing chronologic age. Whereas only 4% of deaths in the first 3 days of life were attributed to infection, 45% of deaths after 2 weeks were related to infection. CONCLUSIONS: Late-onset sepsis is a frequent and important problem among VLBW preterm infants. Successful strategies to decrease late-onset sepsis should decrease VLBW mortality rates, shorten hospital stay, and reduce costs.

Age of Onset↗
PubMed1998

GTP-binding protein mediated phospholipase A2 activation in rat liver during the progression of sepsis.

Effects of GTP-binding proteins on the activation of secretory phospholipaseA2 (sPLA2) and cytosolic phospholipaseA2 (cPLA2) in rat liver during two different phases of sepsis were studied. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 h, respectively, after CLP. The results show that in the absence of G-protein modulator, hepatic sPLA2 and cPLA2 activities were activated by 40.8-46 and 91.6-105.8%, respectively, during early and late phases of sepsis. GTPgammaS and fluoroaluminate (AlF4-) stimulated sPLA2 and cPLA2 activities within each experimental group, i.e., control, early sepsis, and late sepsis. The GTPgammaS and AlF4(-)-stimulated sPLA2 and cPLA2 activities remained significantly elevated during early phase (22.3-65.6% increase) and late phase (32.5-109.1% increase) of sepsis. Further analyses demonstrate that cholera toxin significantly stimulated sPLA2 and cPLA2 activities within each experimental group, and that the cholera toxin stimulated sPLA2 and cPLA2 activities remained significantly higher during early phase (23.5-37% increase) and late phase (56.7-70% increase) of sepsis. In contrast, pertussis toxin significantly inhibited sPLA2 and cPLA2 activities within each experimental group, and that the pertussis toxin-inhibited sPLA2 and cPLA2 activities remained significantly higher in early septic (57-68.5% increase) and late septic (34.6-45.5% increase) experiments. These data demonstrate that cholera toxin-sensitive G alpha s and pertussis toxin-sensitive G alpha i were both involved in the activation of sPLA2 and cPLA2 activities in rat liver during the progression of sepsis.

Animals↗
PubMed2006

A study of the role of multiple site blood cultures in the evaluation of neonatal sepsis.

BACKGROUND: The optimal number of blood cultures needed to document sepsis in an ill neonate has undergone little critical evaluation. Multiple site cultures may improve pathogen detection if intermittent bacteremia occurs, or if a low density of bacteria is present in the blood. We hypothesized, however, that bacterial clearance is slower and bacteremia more continuous in septic neonates, so that a single site blood culture should be sufficient to accurately document true septicemia. OBJECTIVE: To determine the need for multiple site blood cultures in the evaluation of neonates for sepsis. DESIGN/METHODS: Clinical data were prospectively collected for 216 neonates who had 269 pairs of blood cultures taken from two different peripheral sites for the evaluation of possible sepsis. A minimum of 1 ml of blood was obtained from the two peripheral sites within 15-30 min of each other. Based on prior retrospective data, we determined that 203 infants would need to have two site blood cultures to demonstrate a significant improvement in pathogen detection at an alpha of 0.05 and a beta of 0.20 (80%) power. RESULTS: A total of 186 culture pairs were taken for evaluation of early-onset sepsis in 186 neonates, while 83 pairs were drawn for evaluation of late-onset sepsis in 43 neonates. In all, 21 neonates from the late-onset group were evaluated more than once, and 12 neonates were evaluated for both early- and late-onset sepsis. In all, 20 (9.2%) of 216 neonates had 22 episodes of culture-proven sepsis at a median age of 18 days. All neonates with positive cultures had the same organism with a similar sensitivity pattern obtained from the two different peripheral sites. The other 196 study neonates had negative blood cultures from both sites. The single episode of early-onset sepsis was caused by Listeria monocytogenes, while all remaining episodes were late-onset with the following organisms: Staphylococcus epidermidis (7), methicillin-resistant Staphylococcus aureus (MRSA) (3), combined MRSA and Candida albicans (2), Candida albicans alone (2), late-onset Group B beta-hemolytic Streptococcus (GBS) (2), Klebsiella pneumoniae (2), Enterococcus fecalis (1), Escherichia coli (1), and Serratia marcescens (1). Since no infant grew organisms from only one of the two sites, the data indicate that the diagnosis of sepsis would have been made correctly in all infants with a single site culture. CONCLUSIONS: Two site blood cultures for the initial evaluation of neonatal sepsis do not have a better yield in pathogen detection. Sepsis in neonates can be detected with no loss of accuracy with a single site blood culture with blood volume of>or=1 ml.

Bacteremia↗
PubMed2000

Sepsis in children.

BACKGROUND: Sepsis remains lethal to children. At our institution, we have noted that approximately 2% of all hospitalized patients have had sepsis. In the present study, we analyzed episodes of sepsis that occurred in our ward. METHODS: Sepsis that occurred in our institution between January 1984 and December 1998 was reviewed and analyzed. RESULTS: Three hundred and sixty-six episodes of sepsis in 244 admitted patients were analyzed. Sepsis occurred in approximately 2% of all hospitalized patients. Forty-three of 244 patients were under 1 year of age. Eighty-seven percent (212/244) of cases had underlying diseases. Hematologic disorders or neoplasms were the most common underlying disease, comprising 55% of all patients (133/244). Two-hundred and fifty-one of 366 episodes of sepsis were acquired during hospitalization. We identified 409 causative agents. There were 25 polymicrobial infections (25/366; 7%). Gram-positive bacteria comprised 68% of all organisms (280/409). Staphylococcus aureus was the most common organism, comprising 18% of causing agents (75/409). Sixty-six organisms came from the insertion of a central venous catheter. Eighty-one patients experienced recurrent episodes of sepsis. In terms of complications, respiratory distress was the most common complication (36 episodes) and there were 15 episodes of shock. Thirty-seven patients died of sepsis. Sepsis caused by Gram-negative bacteria showed significantly higher mortality than Gram-positive bacteria (11/43 (26%) vs 15/146 (10%); P= 0.053). CONCLUSIONS: In our institution, approximately 20% of septic patients were under 1 year of age and 90% had underlying diseases. The causative agents of sepsis affected the outcome.

Adolescent↗
PubMed1996

Circulating erythropoietin and interleukin-6 concentrations increase in critically ill children with sepsis and septic shock.

OBJECTIVES: To investigate a possible relationship between plasma erythropoietin and interleukin-6 (IL-6) in critically ill children with sepsis or septic shock. To examine the modulatory effects of plasma from these patients on erythropoietin production in vitro, employing a cell culture system that uses the erythropoietin-producing Hep 3B cell line. DESIGN: A prospective, controlled clinical and laboratory study. SETTING: A pediatric intensive care unit and research laboratory facility at a children's hospital. PATIENTS: Children admitted to the pediatric intensive care unit with the diagnosis of sepsis or septic shock (n = 16), and control patients without infection or anemia (n = 16) were admitted to the study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained from 16 children with sepsis or septic shock, and 16 age-matched controls. Plasma erythropoletin and IL-6 concentrations were measured using an enzyme-linked immunoassay. Plasma erythropoietin concentrations were significantly higher in children with sepsis or septic shock (120 +/- 26 mlU/mL) than in controls (10 +/- 2 mlU/mL) (p < .001). Plasma IL-6 concentrations were greater in children diagnosed with sepsis or septic shock (12,405 +/- 6662 pg/mL) than in control patients (7 +/- 1 pg/mL) (p < .001), and higher in septic shock patients (27,469 +/- 13,647 pg/mL) than sepsis patients (688 +/- 258 pg/mL) (p = .03). Hep 3B cells were incubated under hypoxic conditions in media containing plasma from control patients, or patients diagnosed with sepsis or septic shock. Media concentrations of erythropoietin were measured using an enzymelinked immunoassay. Hep 3B cells incubated with plasma from patients diagnosed with sepsis or septic shock produced more erythropoietin (216 +/- 23 mlU/mL) than Hep 3B cells incubated under the same conditions in media containing plasma from control patients (152 +/- 11 mlU/mL) (p = .04). Hypoxic Hep 3B cell erythropoietin production in media incubated with plasma from patients diagnosed with sepsis or septic shock correlated significantly (although weakly) with plasma IL-6 values from these same patients (p = .03, r2 = .28). CONCLUSIONS: Plasma erythropoietin and IL-6 values are increased in critically ill children with sepsis or septic shock in comparison with controls. The data indicate that one or more plasma factors are responsible for stimulation of hypoxia-induced erythropoietin production in the Hep 3B cell line and suggest a possible role for IL-6 in the regulation of erythropoletin production in critically ill children with sepsis or septic shock.

Adolescent↗
PubMed1999

The patient-related costs of care for sepsis patients in a United Kingdom adult general intensive care unit.

OBJECTIVE: To determine the patient-related costs of care for critically ill patients with severe sepsis or early septic shock. DESIGN: Retrospective, longitudinal, observational study during a 10-month period. SETTING: Adult general intensive care unit (ICU) in a university hospital located in the United Kingdom. PATIENTS: The study population consisted of 213 patients admitted consecutively to the ICU during a 10-month period. Thirty-six patients were identified using standard definitions as having developed sepsis and analyzed by group (according to the day on which sepsis was diagnosed): Group 1 patients were septic at admission to ICU (n = 16); group 2 patients were septic on their second day in the ICU (n = 10); and group 3 patients developed sepsis after their second day in the ICU (n = 10). One hundred and seventy-seven ICU patients without sepsis were used as the comparative group (group 4). INTERVENTIONS: None. MAIN RESULTS: Patient-related costs of care, length of ICU stay, and ICU and hospital mortality rates were compiled. The median daily costs of care for patients in groups 1, 2, and 3 were $930.74 (interquartile range $851.59-$1,263.96); $814.47 ($650.89-$1,123.06), and $1,079.39 ($705.02-$1,295.96), respectively; these were significantly more than the group 4 patient's daily cost of $750.38 ($644.10-$908.55) (p < .01). The median total cost of treating the group 4 patients was $1,666.87 ($979.71-$2,772.03), significantly less than for the patients with sepsis (p < .01). The difference in total costs of care between the sepsis groups was also significant (p < .05), with a group 1 patient costing $3,801.55 ($1,865.28-$11,676.08), a group 2 patient costing $13,089.17 ($5,792.94-$22,235.18), and a group 3 patient costing $17,962.78 ($13,030.83-$28,546.73). Patients in groups 1, 2, and 3 stayed in the ICU for 3.3 days (1.3-11.3), 16.5 days (8.9-22), and 16.1 days (10.9-9), respectively. Significant differences were found among the three groups (p < 0.05), as well as between the patients with sepsis and those without (p < 0.001), whose median length of stay was 1.9 days (0.9-3.6). The ICU mortality rates were 50% each for groups 1 and 2, 60% for group 3, and 20% for group 4. Only one patient with sepsis and 16 patients without sepsis died in the hospital ward, producing overall mortality rates of 56% for group 1 and 29% for group 4. CONCLUSIONS: Patients with severe sepsis or early septic shock had a high mortality rate, spent prolonged periods of time in the ICU, and were significantly more expensive to treat than nonsepsis ICU patients.

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PubMed2002

Systemic neuropeptide levels as predictive indicators for lethal outcome in patients with postoperative sepsis.

OBJECTIVES: To document changes in serum levels of the vasoactive and immunoregulatory neuropeptides, calcitonin gene-related peptide (CGRP) and substance P, in human postoperative sepsis and to determine whether levels correlate with outcome. DESIGN: Prospective, descriptive cohort study with no interventions. SETTING: Surgical intensive care unit and clinical research center. PATIENTS: The study included 61 patients with sepsis after major visceral surgery (survivors, n = 37; nonsurvivors, n = 24) and 23 control patients without sepsis. MEASUREMENTS AND MAIN RESULTS: Serum levels of CGRP and substance P were measured by specific enzyme-linked immunoassays over the course of sepsis. Postoperative sepsis was associated with a significant increase in CGRP serum levels. Systemic CGRP levels were significantly higher in nonsurvivors than in survivors as early as day 1 of sepsis and remained significantly elevated in nonsurvivors throughout the entire course of sepsis. Substance P levels were also elevated in sepsis patients as compared with controls, but significant differences between survivors and nonsurvivors were only observed during the final phase of sepsis. CONCLUSIONS: High systemic CGRP levels were associated with lethal outcome already at the onset of sepsis, whereas high substance P levels were identified as late predictive indicators of lethal outcome. These results are consistent with the view that the neuropeptides, CGRP and substance P, may be involved in the pathogenesis of sepsis.

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