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PubMed1998

Tumor necrosis factor binding protein improves incisional wound healing in sepsis.

BACKGROUND: Sepsis is associated with poor wound healing; however, the exact role of tumor necrosis factor (TNF) as a mediator of sepsis-induced alterations in different types of tissue repair is unknown. This study examines the effects of a specific TNF antagonist (TNFbp) on the healing of intestinal anastomoses, incisional wounds, and polyvinyl (PVA) sponge implants in chronic abdominal sepsis. METHODS: Three groups of male Sprague-Dawley rats were studied: control, sepsis, and sepsis + TNFbp. Jejunal resection and anastomosis were performed through a 4-cm upper midline incision on day 1. On day 3, sepsis was induced by creation of a chronic abdominal abscess. Saline (0.1 ml) or TNFbp (1.0 mg/kg, 0.1 ml) was injected subcutaneously every day starting 4 h prior to sepsis. On day 7, the wound-breaking strength (WBS) of the skin incision and intestinal anastomoses was determined using a tensiometer. Wound histology and collagen deposition were evaluated by comparison of Sirius red-stained sections. The hydroxyproline content of PVA sponges was used to quantitate collagen content under the different experimental conditions. RESULTS: Septic mortality (20% vs 26%) was not significantly altered by TNFbp. Septic animals demonstrated a reduction in food consumption on days 3 to 5 that was not affected by TNFbp administration. Neither sepsis nor TNFbp altered the breaking strength or histologic appearance of intestinal anastomoses. However, the breaking strength of incisional wounds was decreased by 40% in septic rats (P < 0.001 vs controls). Administration of TNFbp to septic rats significantly improved incisional WBS (P < 0.01 vs sepsis), but not to control levels. Serius red staining of incisional wounds and PVA sponges demonstrated a decrease in collagen organization and deposition in septic rats that was ameliorated by TNFbp. Similarly, the reduction in hydroxyproline content of PVA sponges from septic animals was prevented by TNFbp. CONCLUSIONS: The process of tissue repair in intestine and skin wounds appears to be significantly different following the septic insult. The healing of jejunal anastomoses was refractory to the catabolic effects of sepsis. In contrast, collagen deposition and organization are significantly decreased in cutaneous wounds during chronic sepsis. TNFbp significantly ameliorated the inhibitory effects of sepsis on cutaneous wound healing. These results suggest that TNF is an important mediator of the decrease in collagen deposition observed in cutaneous wounds during the septic state.

Anastomosis, Surgical↗

PubMed2003

The costs of septic syndromes in the intensive care unit and influence of hospital-acquired sepsis.

OBJECTIVE: To document the costs and outcomes of the various forms of the septic syndromes [systemic inflammatory response syndrome (SIRS), sepsis, severe sepsis, septic shock), particularly those associated with infection acquired in an intensive care unit (ICU). DESIGN: Prospective data collection for all septic patients admitted to a medical ICU during a 1-year period. Costs were computed from the viewpoint of the hospital. RESULTS: Mean total hospital costs were Euro 26,256, Euro 35,185, and Euro 27,083 for patients with sepsis, severe sepsis, and septic shock, respectively. Total costs varied slightly according to the site of infection and the severity of sepsis but were influenced mostly by its mode of acquisition: patients having sepsis associated with ICU-acquired infection incurred total costs about three times those of patients presenting with infection and sepsis on ICU admission (from Euro 39,908 in patients with ICU acquired sepsis to Euro 44,851 in patients with ICU-acquired septic shock). Stratifying patients by the presence of ICU-acquired infection also showed that a first episode of infection complicated by ICU-acquired sepsis incurred at least 2.5 times more costs than a single episode of sepsis. CONCLUSIONS: In this series the medical costs of sepsis were not markedly influenced by its severity but by its mode of acquisition. Due to wide variations in ICU costs cost-effectiveness analyses of treatments for sepsis should document the case-mix of patients and the contribution to this of nosocomial infections.

Costs and Cost Analysis↗

PubMed2000

Immunohistochemical expression of E-selectin in sepsis-induced lung injury.

The vascular endothelium controls leukocyte extravasation into tissue by the induction and modulation of endothelial cell adhesion molecules, such as E-selectin (CD62E). E-selectin is not expressed by non-stimulated endothelium, but is activated by cytokines and initiates neutrophil recruitment in sepsis-induced lung injury. The aim of the present study was to assess the value of the immunohistochemical expression of endothelial E-selectin for the post-mortem differentiation between death due to sepsis and death due to other causes. The immunohistochemical expression of E-selectin was investigated in lung specimens obtained at autopsy from sepsis-associated fatalities (n = 6), possible sepsis-associated fatalities (n = 7), non-sepsis group I (death due to unnatural causes, e.g. trauma, electrocution, drowning, hanging n = 17) and non-sepsis group II fatalities (death due to natural causes, e.g. myocardial infarction, intracerebral bleeding n = 7). E-selectin was detected in paraffin sections using the ABC technique and the expression was scored semiquantitatively by evaluating the intensity and incidence of positively stained endothelium of the interstitial pulmonary microvasculature. E-selectin was strongly expressed in all cases of the definite sepsis group, in 29% of the possible sepsis-associated fatalities and in only 4% of the cases in the non-sepsis groups I and II. In comparison to all other study groups, E-selectin expression in the definite sepsis group differed significantly (p < 0.05). Cases with inflammatory and mechanical lung tissue alterations from the control groups showed no positive immunohistochemical reaction for E-selectin; therefore, false positive results should not be expected in non-sepsis cases. Our findings suggest that the immunohistochemical detection of an intense expression of E-selectin in lung tissue may prove to be a valuable diagnostic tool in the forensic post-mortem elucidation of death due to sepsis.

Adult↗

PubMed2005

Oxidative parameters differences during non-lethal and lethal sepsis development.

BACKGROUND: The participation of oxidative stress in the development of sepsis is still unclear. The aim of this study was to determine which aspect of antioxidant/pro-oxidant has the major importance in differentiation between non-lethal and lethal sepsis. MATERIALS AND METHODS: Non-lethal and lethal sepsis were induced by cecal ligation and puncture (CLP) in adult Wistar rats, using 18 and 14 gauge needle, respectively. Rats were sacrificed within 12, 24, 48, and 96 h and organs (heart, lung, diaphragm, liver, and kidney) were isolated. The main antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) were measured, as well as protein carbonyls and TBARS, as an index of oxidative damage. RESULTS: Twelve hours after lethal sepsis induction we observed an increase in the oxidative damage in all of the organs studied. In contrast, during non-lethal sepsis, the oxidative damage occurs late in the course of the disease (after 48 h) and the increase in protein carbonyls is of less magnitude when compared to the lethal sepsis. During non-lethal sepsis, in contrast to the lethal sepsis, there is no sustained increase in the SOD/CAT relation. CONCLUSIONS: The present study is the first report showing a different profile of oxidative damage when comparing non-lethal and lethal sepsis. The oxidative damage in proteins seems to be a differential parameter between non-lethal and lethal sepsis. In addition, the SOD/CAT imbalance seems to be an important factor in the oxidative stress during the lethal sepsis, but seems not to happen, in a sustained way, during the non-lethal sepsis.

Animals↗

PubMed1997

Changes of adenosine triphosphate-dependent calcium uptake in microsomal fractions of rat liver during sepsis.

BACKGROUND: Intracellular calcium concentration is an important regulator of cellular metabolism. Endoplasmic reticulum membranes play an important role in the regulation of cytoplasmic calcium in the mammalian liver. The characterization of the changes of calcium uptake in endoplasmic reticulum may contribute to the potential intracellular mechanisms for cellular dysfunction during sepsis. METHODS: The effects of sepsis on the calcium uptake in rough endoplasmic reticulum of rat liver were studied. Sepsis was induced by means of cecal ligation and puncture (CLP). The control rats underwent sham operation. Microsomal fractions were isolated from the liver with differential centrifugation. RESULTS: The calcium uptake by liver endoplasmic reticulum was decreased by 30% to 35% (p < 0.05) during early sepsis (9 hours after CLP) and by 38% to 43% (p < 0.05) during late sepsis (18 hours after CLP), respectively. The maximum velocity values for adenosine triphosphate (ATP) and for Ca2+ were also decreased by 25% to 37% (p < 0.05) during early sepsis and by 35% to 42% (p < 0.05) during late sepsis. The Michaelis-Menten constant for ATP and Ca2+ transport had no difference among three groups. The magnesium stimulation and vanadate inhibitory activity were also decreased by 17% to 38% (p < 0.05) during early sepsis and by 34% to 50% (p < 0.05) during late sepsis. CONCLUSIONS: These data demonstrate that ATP-dependent calcium uptake in rough endoplasmic reticulum of rat liver was impaired during early and late sepsis. Because the low intracellular calcium concentration plays an important role in the regulation of cellular function, an impairment in the ATP-dependent calcium uptake by endoplasmic reticulum during early and late sepsis may have a pathophysiologic significance in contributing to the development of altered hepatic metabolism during sepsis.

Adenosine Triphosphate↗

PubMed1998

Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation.

BACKGROUND: Neonatal sepsis is a common and life-threatening disorder, particularly among preterm infants. Early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non-specific and there are no reliable early laboratory indicators. We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), and circulating intercellular adhesion molecule-1 (cICAM-1) before clinical diagnosis of sepsis. METHODS: In a prospective multicentre study, we monitored 182 very-low-birthweight infants in six intensive-care units for occurrence of sepsis. During routine or clinically indicated blood sampling, an additional sample was collected for measurement of IL-1ra, IL-6, cICAM-1, and C-reactive protein (CRP). Infants were grouped into those with proven sepsis, no infection, or unclassified. The mean study duration was 34 days. Whenever sepsis occurred, a study period of 10 days was defined: day 0 was the day of clinical diagnosis of sepsis; days -4 to -1 were the 4 days before diagnosis; days +1 to +5 were the 5 days after. We compared the concentrations of the immune mediators during the 10-day study period with group-specific baseline values from before day -4. FINDINGS: 101 infants were included in the analysis: 21 with proven sepsis, 20 with no infection, and 60 unclassified. We excluded 57 because of incomplete datasets and 24 who had early-onset sepsis. IL-1ra and IL-6 increased significantly 2 days before diagnosis of sepsis; maximum median increases within the study period were 15-fold for IL-1ra and 12-fold for IL-6. The diagnostic sensitivities of IL-1ra, IL-6, and CRP concentrations on day 0 of diagnosis were 93%, 86%, and 43%, respectively; corresponding values on day -1 were 64%, 57%, and 18%. The specificities of IL-1ra, IL-6, and CRP concentrations were 92%, 83%, and 93%. cICAM-1 had a specificity of only 64%. INTERPRETATION: IL-1ra and IL-6 are superior to cICAM-1 and CRP as predictors of sepsis 1 or more days before clinical diagnosis. Ad-hoc measurement of these cytokines could allow earlier initiation of antibiotic therapy with corresponding improvement in outcome in very-low-birthweight infants with sepsis.

Austria↗

PubMed2002

The role of intrapartum fever in identifying asymptomatic term neonates with early-onset neonatal sepsis.

OBJECTIVE: To assess the role of intrapartum fever in identifying asymptomatic term neonates with early-onset neonatal sepsis. STUDY DESIGN: Retrospective review of all term neonates with sepsis over a 7-year period to evaluate the significance of symptoms at delivery and intrapartum sepsis risks factors in identifying neonates with sepsis. RESULTS: Fifty-three of 90 term neonates with sepsis (59%) were asymptomatic at delivery. Thirty-five of 53 asymptomatic term neonates (66%) met criteria for sepsis evaluations and 18 (34%) were evaluated when symptoms developed after delivery. Among the 35 asymptomatic term neonates meeting criteria for sepsis evaluations, 14 (40%) had evaluations because of intrapartum fever. Thus, 14 of 53 (26%) asymptomatic term neonates with sepsis (30% of GBS sepsis and 11% of non-GBS sepsis) would not have been evaluated if intrapartum fever were ignored. CONCLUSION: Over half of term neonates with sepsis were asymptomatic at delivery. Intrapartum fever was helpful in identifying over a quarter of asymptomatic term neonates with sepsis.

Delivery, Obstetric↗

PubMed2003

Severe sepsis and septic shock: defining the clinical problem.

It is generally acknowledged that severe sepsis/septic shock is a major problem in clinical medicine, yet the extent of the problem and its basic immunology remain poorly defined. The generation of accurate statistics about sepsis is confounded by the imprecise and highly variable terminology used to describe sepsis by clinicians around the world. The problem of sepsis is further complicated by the remarkably diverse spectrum of illness encompassed under the term 'sepsis'. Sepsis may range in severity from mild systemic inflammation without significant clinical consequences to multisystem failure in septic shock with an exceedingly high mortality rate. Sepsis connotes a clinical syndrome that may occur in any age group, in markedly different patient populations, and in response to a multitude of microbial pathogens from multiple different anatomical sites within the human body. A concerted effort has been made to standardize definitions of sepsis by the use of international committees and consensus opinions from panels of experts in sepsis research. While consensus definitions of sepsis have proven to be of value, the lack of uniformity in interpretation of these definitions continues to be problematic by clinicians and basic researchers alike. Recently, a new conceptual framework for understanding sepsis has been developed, called the PIRO concept (predisposition, infection, response and organ dysfunction). This has been conceptually modeled from the TNM classification (tumor size, nodal spread, metastases) which has been successfully used in defining treatment and prognostic indicators in clinical oncology. Further refinements in the definitions and predisposing factors of severe sepsis should improve the understanding and management of severe sepsis and septic shock in the near future.

Adult↗

PubMed2006

Tissue bioenergetics and microvascular perfusion are impaired in rat ileal mucosa in normotensive sepsis.

OBJECTIVE: Sepsis is a systemic inflammatory response to a bacterial infection. Inflammation may result in injury to the small bowel and an increase in translocation of bacteria and toxins across the mucosal barrier, which may contribute to the progression of sepsis. Microcirculatory perfusion or cytopathic hypoxia may cause impairment of tissue bioenergetics and injury in sepsis. The objective of this study was to determine if sepsis is associated with microcirculatory hypoperfusion and impaired tissue bioenergetics in the ileal mucosa. MATERIALS AND METHODS: Sprague-Dawley rats were randomized to cecal ligation and perforation (sepsis group, n = 12) or control group (n = 14) and received arterial and venous catheters and fluid resuscitation. Following 24 h, rats were anesthetized with isoflurane and the ileum was prepared for intravital microscopy. Images of NADH fluorescence, which is an index of tissue bioenergetics, central arterial diameter, red cell velocity, red cell flux, and average intercapillary area, were recorded in 6-9 villi in each rat. RESULTS: Central arterial red cell flux (control 277 +/- 30 cell/s, sepsis 108 +/- 13 cells/s, p < .05), diameter (control 10.4 +/- 0.4 microm, sepsis 8.2 +/- 0.3 microm, p < .05) and red cell velocity (control 590 +/- 47 microm/s, sepsis 449 +/- 63 microm/s, p < .05) were decreased while average intercapillary area (control 815 +/- 171 microm(2), sepsis 1412 +/- 364 microm(2), p < .05) and NADH fluorescence (control 116 +/- 6 AIU, sepsis 154 +/- 9 AIU, p < .05) were increased at the villus tip in the sepsis group. CONCLUSION: Sepsis is associated with bioenergetic impairment and capillary hypoperfusion at the villus tip and a decrease in red cell flux in the central arteriole.

Animals↗

PubMed2002

Novel approach to prevent the transition from the hyperdynamic phase to the hypodynamic phase of sepsis: role of adrenomedullin and adrenomedullin binding protein-1.

OBJECTIVE: To determine whether the combined administration of adrenomedullin and adrenomedullin binding protein-1 (AM/AMBP-1) has any modulatory effects on the cardiovascular response during the progression of sepsis. SUMMARY BACKGROUND DATA: Polymicrobial sepsis is characterized by an early, hyperdynamic phase followed by a late, hypodynamic phase. Recent studies have shown that AM, a newly reported potent vasodilator peptide, plays a major role in initiating the hyperdynamic response. Moreover, the reduced vascular responsiveness to AM appears to be responsible for the transition from the hyperdynamic phase to the hypodynamic phase of sepsis. Although the novel AMBP-1 augments AM-mediated action in vitro, it remains unknown whether AM/AMBP-1 maintains vascular responsiveness to AM at the late stage of sepsis. METHODS: Sepsis was induced by cecal ligation and puncture (CLP) in adult male rats. Human AMBP-1 (40 microg/kg body weight) was infused intravenously at the beginning of sepsis for 20 minutes and synthetic AM (12 microg/kg body weight) was continuously administrated for the entire study period using an Alzert micro-osmotic pump, beginning 3 hours before the induction of sepsis. At 20 hours after the onset of sepsis (i.e., the late stage), cardiac output, systemic oxygen delivery, stroke volume, total peripheral resistance, and organ blood flow in the liver, gut, kidneys, and heart were determined using radioactive microspheres. Plasma levels of transaminases (ALT, AST) and lactate were also measured. Additional studies were conducted to determine whether administration of AM alone or AMBP-1 alone alters the cardiovascular response at 20 hours after CLP. In additional rats, the necrotic cecum was excised at 20 hours after CLP following AM/AMBP-1 treatment, the peritoneal cavity irrigated with saline, and the midline incision closed in layers. Survival was then examined for a period of 10 days thereafter. RESULTS: Administration of AM/AMBP-1 prevented the decrease in the measured systemic and regional hemodynamic parameters at 20 hours after the onset of sepsis. Moreover, AM/AMBP-1 significantly attenuated hepatic damage and the elevation of plasma lactate, and prevented hemoconcentration. Treatment with AM/AMBP-1 reduced the overall 10-day mortality rate from 57% to 7%. Neither AM nor AMBP-1 alone was sufficient to maintain cardiovascular stability at 20 hours after CLP. CONCLUSIONS: Since AM/AMBP-1 delays or even prevents the transition from the hyperdynamic phase to the hypodynamic phase of sepsis, attenuates tissue injury, and decreases sepsis-induced morality, these agents should provide a novel approach for maintaining cardiovascular stability and preventing cell and organ damage during the progression of polymicrobial sepsis.

Adrenomedullin↗

PubMed2000

Coagulation system and platelets are fully activated in uncomplicated sepsis.

OBJECTIVE: To test the hypothesis that the coagulation system and platelets are activated in sepsis, the uncomplicated and usually earliest stage of the septic process, and to compare the findings detected in sepsis with those found in severe sepsis and septic shock. DESIGN: Prospective study comparing patients with sepsis, severe sepsis, and septic shock, and healthy volunteers. SETTING: General intensive care unit in a tertiary university hospital. PATIENTS: Seventy-four consecutive septic patients (45 with sepsis, 15 with severe sepsis, and 14 with septic shock). Fourteen healthy volunteers served as control subjects. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: After blood sampling, molecular activation markers of coagulation (prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin) and of platelets (beta-thromboglobulin and platelet factor 4), several coagulation factors, global tests of coagulation (prothrombin time and activated partial thromboplastin time), and platelet count (PTL) were measured. In sepsis, prothrombin fragments 1 and 2, fibrinopeptide A, thrombin-antithrombin complexes, and monomers of fibrin were increased to 2.52+/-0.21 nmol/L, 20.88+/-2.52 ng/mL, 33.8+/-2.9 microg/L, and 69% positive, respectively, compared with control subjects (0.86+/-063 nmol/L, 1.14+/-0.15 ng/mL, 16.07+/-1.01 microg/L, and 0%, respectively). Beta-Thromboglobulin and the beta-thromboglobulin-to-platelet factor 4 ratio were also increased to 107.87+/-11.87 IU/mL and 8.86+/-1.06, compared with controls (18.36 +/-2.99 IU/mL and 2.67+/-0.52, respectively). With the exception of a decrease in factor XII and an increase in fibrinogen, coagulation factors, global coagulation tests, and PTL were not changed in sepsis. In severe sepsis and mainly in septic shock, coagulation factors were markedly decreased, global coagulation tests were prolonged, and PTL was reduced. All changes were independent of the causative infectious pathogen. CONCLUSION: Coagulation system and platelets are strongly activated in sepsis. In this stage, only factor XII is decreased. In contrast, in severe sepsis and mainly in septic shock, most of the coagulation factors are depleted, PTL is decreased, and global coagulation tests are prolonged, indicating exhaustion of hemostasis. Finally, Gram-positive, Gram-negative, and other microorganisms produce identical impairment of coagulation.

Adolescent↗

PubMed2001

The hypothalamic-pituitary-adrenal axis of patients with severe sepsis: altered response to corticotropin-releasing hormone.

OBJECTIVE: To investigate the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis in patients with severe sepsis by stimulating with corticotropin-releasing hormone (CRH). DESIGN: Prospective observational study in consecutive intensive care unit patients with severe sepsis. SETTING: Surgical intensive care unit and outpatient department of endocrinology in a university hospital. PATIENTS: The study included 20 patients with the diagnosis of severe sepsis; six critically ill, nonseptic patients after major surgery; ten patients with primary adrenal insufficiency; ten patients with anterior pituitary insufficiency; and ten individuals without clinical signs of HPA axis disturbance. INTERVENTIONS: CRH tests were performed with an intravenous bolus injection of 100 microg of human CRH. MEASUREMENTS AND MAIN RESULTS: We studied the functional integrity of the HPA axis in patients with severe sepsis by performing the CRH test. In addition, during the period of severe sepsis, we repeatedly measured basal plasma concentrations of adrenocorticotropin hormone (ACTH) and cortisol. The mean basal plasma cortisol concentration was decreased significantly in nonsurvivors with severe sepsis (288.8 +/- 29.1 [sem] nmol/L) compared with survivors (468.1+/- 18.6 nmol/L; p <.01). By calculating the ACTH/cortisol indices, we found no evidence for adrenal insufficiency in patients with severe sepsis. The mean ACTH/cortisol indices of nonsurvivors with severe sepsis (0.02 +/- 0.008) and survivors (0.01 +/- 0.002) were significantly lower compared with the index of patients with primary adrenal insufficiency (6.8 +/- 1.0; p <.001). In contrast, in nonsurvivors with severe sepsis, the plasma cortisol response to CRH stimulation was impaired compared with survivors: The mean basal cortisol concentration within the CRH test was 269.4 +/- 39.8 nmol/L in nonsurvivors compared with 470.8 +/- 48.4 nmol/L in survivors and increased to a peak value of 421.6 +/- 72.6 nmol/L in nonsurvivors and 680.7 +/- 43.8 nmol/L in survivors (p <.02). However, the change in plasma cortisol, expressed as mean +/- sem and calculated by subtracting the basal cortisol from the peak cortisol after CRH stimulation, was not significantly different in survivors with severe sepsis (243.5 +/- 36.1, range 111.0-524.0 nmol/L, n = 15) compared with nonsurvivors (161.0 +/- 38.9, range 42.0-245.0 nmol/L, n = 5; p >.05). CONCLUSIONS: We found lower basal plasma cortisol concentrations in nonsurvivors compared with survivors of severe sepsis. In addition, the plasma cortisol response to a single CRH stimulation was impaired in nonsurvivors compared with survivors. Reduced responses to CRH stimulation may reflect a state of endocrinologic organ dysfunction in severe sepsis.

Adolescent↗

PubMed2003

Procalcitonin is persistently increased among children with poor outcome from bacterial sepsis.

OBJECTIVE: To examine the relationships between procalcitonin, bacterial infection, sepsis-induced multiple organ failure, and mortality rate in children. DESIGN: Cohort study. SETTING: A multidisciplinary, tertiary-care pediatric intensive care unit. PATIENTS: Seventy-eight children meeting criteria for sepsis or septic shock and 12 critically ill children without sepsis. INTERVENTIONS: Venous or arterial blood sampling. MEASUREMENTS AND MAIN RESULTS: 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. CONCLUSIONS: 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.

Adolescent↗

PubMed2003

Adrenocortical hormones in survivors and nonsurvivors of severe sepsis: diverse time course of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol.

OBJECTIVE: Activation and suppression of immune responses are crucial events during sepsis. Based on substantial new data, a complex picture of differential immune-enhancing and immunosuppressive actions of adrenocortical steroids is emerging. The adrenal androgen dehydroepiandrosterone and its precursor, dehydroepiandrosterone-sulfate, show a considerable decrease with increasing age and serve as functional antagonists to endogenous glucocorticoids. Therefore, we examined time-dependent changes in dehydroepiandrosterone, dehydroepiandrosterone-sulfate, cortisol, adrenocorticotropin, and inflammatory variables in surviving and nonsurviving patients with severe sepsis. DESIGN: Prospective observational study in consecutive patients. SETTING: Medical and interdisciplinary intensive care units in two university hospitals and one city hospital. PATIENTS: Thirty nonsurgical patients (25 men and 5 women) with severe sepsis (American College of Chest Physicians/Society of Critical Care Medicine criteria); 15 survivors (mean age, 54 +/- 14 yrs; Acute Physiology and Chronic Health Evaluation III score, 59 +/- 35) and 15 nonsurvivors (mean age, 63 +/- 15 yrs; Acute Physiology and Chronic Health Evaluation III score, 67 +/- 24) were included. Hormones were compared individually and between survivors/nonsurvivors by sequential blood drawings from early sepsis till time of recovery/death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During early sepsis, cortisol (nmol/L) was not significantly higher in survivors than nonsurvivors (750 +/- 121 vs. 454 +/- 92, p <.08) and decreased in survivors (p <.01) during late sepsis. During early sepsis, dehydroepiandrosterone-sulfate (percentage of age-matched normal levels) was higher in survivors than nonsurvivors (85 +/- 19 vs. 22 +/- 7, p <.01). Dehydroepiandrosterone-sulfate decreased in survivors (p =.0001) but remained low in nonsurvivors during late sepsis. Dehydroepiandrosterone (percentage of age-matched normal levels) was not significantly elevated in survivors compared to nonsurvivors during early sepsis (282 +/- 42 vs. 214 +/- 63, p <.08). Dehydroepiandrosterone decreased in survivors (p <.01) but not in nonsurvivors during late sepsis. Linear regression for dehydroepiandrosterone levels showed a reconstitution of age dependence only in survivors during recovery. Adrenocorticotropin levels did not change. The dehydroepiandrosterone-sulfate/cortisol ratio decreased significantly in both survivors and nonsurvivors, whereas dehydroepiandrosterone/cortisol ratio only decreased in survivors during course of sepsis. CONCLUSIONS: During sepsis, adrenal androgens and glucocorticoids show a diverse time-dependent course in survivors and nonsurvivors.

APACHE↗

PubMed2005

Scope and epidemiology of pediatric sepsis.

OBJECTIVE: To summarize the scope and epidemiology of pediatric sepsis. DESIGN: Review of published literature. RESULTS: Sepsis is a leading cause of death in infants and children, with >42,000 cases of severe sepsis annually in the United States and millions worldwide. Half of the children with severe sepsis in the United States are infants, and half of infants are low- or very low-birth-weight babies. Underlying disease occurs in 49% of U.S. children with severe sepsis. National hospital costs associated with severe sepsis in the United States were $2.3 billion in 1999. Relatively simple strategies to identify and treat children with sepsis in the developing world have shown remarkable success. These strategies have included empirical antibiotics in babies at high risk of sepsis and aggressive fluid resuscitation in Dengue hemorrhagic fever. CONCLUSIONS: Sepsis is a major health problem among children in both developing and industrialized countries. However, sepsis is both preventable and treatable. Improved prevention and treatment of sepsis could have a substantial effect on survival and quality of life of all children, both those who are otherwise healthy and those who are chronically ill. The variations in the epidemiology of pediatric sepsis underscore the need for a multidisciplinary approach and consistently applied definitions.

Adolescent↗

PubMed2025

Causal associations between inflammatory bowel disease and sepsis: a two-sample Mendelian randomization study.

BACKGROUND: Recent observational studies have revealed an inconclusive correlation between inflammatory bowel disease (IBD) and sepsis, accompanied by an uncertain understanding of the causal relationship between the two. To investigate the causality between IBD and sepsis, we employed a two-sample Mendelian randomization (MR) approach. METHODS: A genome-wide significant threshold (P < 5 × 10-8) was achieved in order to identify single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for two types of IBD, such as Crohn's disease (CD) and ulcerative colitis (UC). Subsequently, the selected SNPs were assessed in relation to three categories of sepsis, namely sepsis, sepsis (critical care), and sepsis (28-day death in critical care). An inverse-variance weighted (IVW) estimation of MR was conducted, followed by sensitivity analysis on multiple dimensions. RESULTS: There was a significant association between genetic liability to CD (IVW: OR, 1.246; 95% CI, 1.090-1.423; P = 0.0012) with sepsis (28-day death in critical care), but not with sepsis (critical care) and sepsis. Whereas UC showed slightly, yet statistically insignificant, higher risk for sepsis (IVW: OR, 1.031; 95% CI, 0.988-1.064; P = 0.064). CONCLUSION: Our study offers genetic evidence that supports a substantial causal relationship between CD and sepsis (28-day death in critical care). To enhance the specificity and objectivity of future research findings, it is recommended to specify the types of IBD and the severity of sepsis. Furthermore, the genetic risk loci related may become potential drug development targets.

Humans↗

PubMed2006

The epidemiology of sepsis in patients with malignancy.

STUDY OBJECTIVES: To evaluate the longitudinal epidemiology of sepsis in patients with a history of cancer and to specifically examine sepsis-related disparities in risk or outcome. DESIGN: Sepsis cases from 1979 through 2001 using a nationally representative sample of nonfederal acute-care hospitalizations in the United States (the National Hospital Discharge Survey) integrated with cancer prevalence from the Surveillance, Epidemiology, and End Results database. SETTING: Eight hundred fifty-four million acute-care hospitalizations and 8.9 million patients with cancer. PATIENTS OR PARTICIPANTS: Patients with a history of cancer hospitalized with a diagnosis of sepsis. MEASUREMENTS AND RESULTS: From 1979 to 2001, there were a total of 1,781,445 cases of sepsis in patients with cancer, yielding a mean annual incidence rate of 1,465 cases per 100,000 cancer patients and a relative risk [RR] of 9.77 compared to noncancer patients (95% confidence interval [95% CI], 9.67 to 9.88). In contrast to the absolute number of cases, the incidence rate of sepsis decreased over time, from a peak of 1,959 cases per 100,000 cancer patients in 1987 to 995 cases per 100,000 in 2001. The distribution of infectious sources causing sepsis was associated with the type of malignancy. White cancer patients had a lower risk for sepsis compared to nonwhites (African-American RR, 1.28; 95% CI, 1.16 to 1.40) and other races (RR, 1.47; 95% CI, 1.22 to 1.72); and male cancer patients had a higher risk for sepsis compared to female cancer patients (male RR, 1.17; 95% CI, 1.10 to 1.23). Cancer was an independent predictor of death among sepsis patients by multivariable analysis (adjusted odds ratio for death, 1.98; 95% CI, 1.97 to 1.99). CONCLUSIONS: Patients with a history of cancer are at increased risk for acquiring and subsequently dying from sepsis, compared to the general population, although incidence and fatality rates are decreasing over time. There are significant racial and gender disparities in the incidence and outcome of sepsis among cancer patients that require explanation.

Black or African American↗

PubMed1997

Meta-analyses of the effectiveness of intravenous immune globulin for prevention and treatment of neonatal sepsis.

OBJECTIVE: To determine the effectiveness of intravenous immune globulin (IVIG) in the prevention and treatment of neonatal sepsis. DESIGN: All published studies of IVIG for the prevention or treatment of neonatal sepsis were reviewed. Peer-reviewed, prospective, randomized trials with high merit were analyzed by two meta-analyses. The effect of prophylactic IVIG was evaluated by comparison of the numbers of cases of sepsis (bacteremia in the presence of systemic manifestations of sepsis), and of therapeutic IVIG by comparison of the numbers of deaths resulting from early-onset sepsis. RESULTS: Meta-analysis of 4933 evaluable newborns in 12 studies of IVIG prophylaxis showed a statistically significant negative association with the incidence of sepsis in premature low birth weight newborns given IVIG shortly after birth (P = .0193, two-sided). The heterogeneity across these studies precluded estimation of a common odds ratio. Meta-analysis of 110 evaluable cases of neonatal sepsis in three studies of IVIG treatment of neonatal sepsis showed a significant decrease in the mortality rate for neonates with sepsis given IVIG (P = .007, two-sided). The common odds ratio was .173 (95% confidence interval = .031 to .735). CONCLUSIONS: Using conservative and objective outcome rating criteria, the addition of IVIG to standard therapies is of minimal but demonstrable benefit in preventing sepsis when administered prophylactically to premature low birth weight newborns, and of unequivocal benefit in preventing death when administered therapeutically for early-onset neonatal sepsis. The likelihood of newborns with sepsis living past the neonatal period was improved nearly sixfold when IVIG was administered in addition to standard therapies.

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