Postoperative sepsis in infants below 6 months of age

BACKGROUND: Sepsis is a threatening postoperative complication especially in small infants. Regarding the advances in perinatal medicine, its incidence is unknown to date. We aimed to investigate the incidence, risk factors, laboratory findings and outcome of postoperative sepsis in infants younger than 6 months old. METHODS: We examined postoperative sepsis in babies below 6 months of age during a 4-year period at a tertiary pediatric institution. RESULTS: The rate of postoperative sepsis was 6.9%. Laparotomy with enterotomy, thoracotomy and diaphragmatic hernia repair (P<0.05, respectively) as well as low postnatal age and long operation time (P<0.001, respectively) were correlated with the incidence of sepsis. Significant independent predictors for the development of sepsis were the presence of a central venous catheter and perioperative antibiotic treatment (P<0.001, respectively). Coagulase negative Staphylococci were the major infecting organism associated with postoperative sepsis, accounting for 53% of monomicrobial infections. Complete blood counts with differential were not different between infants with sepsis and controls, who had undergone the same surgical procedures. Outcome was favorable in all cases; however, the length of hospital stay was significantly longer in sepsis patients (P<0.05). CONCLUSIONS: Postoperative sepsis syndrome is a frequent complication in infants below 6 months of age and causes significant prolongation of hospital stay. Adequate prevention and therapeutic strategies warrant further prospective investigations.

Avaliação das alterações macro-hemodinâmicas, microcirculatórias, gasométricas, metabólicas e inflamatórias secundárias à sedação com dexmedetomidina em um modelo experimental de endotoxemia em hamsters

Pela sua alta incidência, morbidade, mortalidade e custos ao sistema de saúde, a sepse se destaca entre as diversas indicações de internação em unidade de terapia intensiva (UTI). A disfunção da microcirculação tem papel central na gênese e manutenção da síndrome séptica, sendo um marco fisiopatológico desta síndrome. Pacientes críticos invariavelmente estão ansiosos, agitados, confusos, desconfortáveis e/ou com dor. Neste contexto, drogas sedativas são amplamente utilizadas na medicina intensiva. A dexmedetomidina, um agonista potente e altamente seletivo dos receptores alfa-2 adrenérgicos, vem conquistando espaço como o sedativo de escolha nas UTIs por seus efeitos de sedação consciente, redução da duração e incidência de delirium e preservação da ventilação espontânea. Apesar destas possíveis vantagens, a indicação de uso da dexmedetomidina na síndrome séptica ainda carece de conhecimentos sobre seus efeitos na microcirculação e perfusão orgânica. Com o intuito de caracterizar os efeitos microcirculatórios da dexmedetomidina em um modelo murino de endotoxemia que permite estudos in vivo da inflamação e disfunção da perfusão microvascular, hamsters Sírios dourados submetidos à endotoxemia induzida por administração intravenosa de lipopolissacarídeo de Escherichia coli (LPS, 1,0 mg.kg-1) foram sedados com dexmedetomidina (5,0 μg.kg.h-1). A microscopia intravital da preparação experimental (câmara dorsal) permitiu a realização de uma análise quantitativa das variáveis microvasculares e do rolamento e adesão de leucócitos à parede venular. Também foram analisados os parâmetros macro-hemodinâmicos e gasométricos (arterial e venoso portal), as concentrações de lactato arterial e venoso portal, a água pulmonar total e a sobrevivência do animal. Animais não-endotoxêmicos e/ou tratados com solução salina a 0,9% serviram como controles neste experimento. O LPS aumentou o rolamento e a adesão de leucócitos à parede venular, diminuiu a densidade capilar funcional e a velocidade das hemácias nos capilares e induziu acidose metabólica. O tratamento com dexmedetomidina atenuou significativamente estas respostas patológicas (p < 0,05). A frequência de pulso dos animais foi significativamente reduzida pela droga (p < 0,05). Outros resultados não foram tão expressivos (estatisticamente ou clinicamente). Estes resultados indicam que a utilização de dexmedetomidina produz um efeito protetor sobre a microcirculação da câmara dorsal de hamsters endotoxêmicos. Efeitos anti-inflamatórios da dexmedetomidina sobre os leucócitos e o endotélio poderiam melhorar a perfusão capilar e representar o mecanismo in vivo de ação da droga na microcirculação.

Bactericidal/permeability-increasing protein attenuates systemic inflammation and acute lung injury in porcine lower limb ischemia-reperfusion injury.

OBJECTIVE: To investigate the role of recombinant bactericidal/permeability-increasing protein (rBPI21) in the attenuation of the sepsis syndrome and acute lung injury associated with lower limb ischemia-reperfusion (I/R) injury. SUMMARY BACKGROUND DATA: Gut-derived endotoxin has been implicated in the conversion of the sterile inflammatory response to a lethal sepsis syndrome after lower torso I/R injury. rBPI21 is a novel antiendotoxin therapy with proven benefit in sepsis. METHODS: Anesthetized ventilated swine underwent midline laparotomy and bilateral external iliac artery occlusion for 2 hours followed by 2.5 hours of reperfusion. Two groups (n = 6 per group) were randomized to receive, by intravenous infusion over 30 minutes, at the start of reperfusion, either thaumatin, a control-protein preparation, at 2 mg/kg body weight, or rBPI21 at 2 mg/kg body weight. A control group (n = 6) underwent laparotomy without further treatment and was administered thaumatin at 2 mg/kg body weight after 2 hours of anesthesia. Blood from a carotid artery cannula was taken every half-hour for arterial blood gas analysis. Plasma was separated and stored at -70 degrees C for later determination of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 by bioassay, and IL-8 by enzyme-linked immunosorbent assay (ELISA), as a markers of systemic inflammation. Plasma endotoxin concentration was measured using ELISA. Lung tissue wet-to-dry weight ratio and myeloperoxidase concentration were used as markers of edema and neutrophil sequestration, respectively. Bronchoalveolar lavage protein concentration was measured by the bicinclinoic acid method as a measure of capillary-alveolar protein leak. The alveolar-arterial gradient was measured; a large gradient indicated impaired oxygen transport and hence lung injury. RESULTS: Bilateral hind limb I/R injury increased significantly intestinal mucosal acidosis, intestinal permeability, portal endotoxemia, plasma IL-6 concentrations, circulating phagocytic cell priming and pulmonary leukosequestration, edema, capillary-alveolar protein leak, and impaired gas exchange. Conversely, pigs treated with rBPI21 2 mg/kg at the onset of reperfusion had significantly reduced intestinal mucosal acidosis, portal endotoxin concentrations, and circulating phagocytic cell priming and had significantly less pulmonary edema, leukosequestration, and respiratory failure. CONCLUSIONS: Endotoxin transmigration across a hyperpermeable gut barrier, phagocytic cell priming, and cytokinemia are key events of I/R injury, sepsis, and pulmonary dysfunction. This study shows that rBPI21 ameliorates these adverse effects and may provide a novel therapeutic approach for prevention of I/R-associated sepsis syndrome.

Febrile response induced by cecal ligation and puncture (CLP) in rats: involvement of prostaglandin E-2 and cytokines

The purpose of the present study was to better understand the events involved in the febrile response induced by cecal ligation and puncture (CLP), a complex infectious process. To this end, we conducted in vivo experiments in rats examining (1) fever development, (2) bacterial number in the infection focus and in blood, (3) peripheral and hypothalamic synthesis of cytokines, (4) hypothalamic and cerebrospinal fluid (CSF) synthesis of prostaglandin E-2 (PGE(2)), (5) the effect of anti-IL-6 antibody on fever, and (6) the effect of celecoxib on fever and hypothalamic synthesis of PGE(2) after CLP induction. We found that CLP promotes fever and animal death depending on the number of punctures. The peak of CLP-induced fever overlapped with the maximal increase in the number of bacteria in the infectious focus and blood, which occurred at 6 and 12 h. The peak of the febrile response also coincided with increased amounts of interleukin (IL)-1 beta, IL-6 and IL-10 in the peritoneal exudate and serum; IL-6 in the hypothalamus and PGE(2) in the CSF and predominantly in the hypothalamus. Moreover, intracerebroventricularly injected anti-IL-6 antibody reduced the febrile response while celecoxib reduced the fever and PGE(2) amount in the hypothalamus induced by CLP. Tumor necrosis factor (TNF)-alpha peaked at 3 h at all sites studied. Conversely, IL-10 concentration decreased in the hypothalamus. These findings show that the peak of CLP-induced fever is accompanied by an increase of bacteria in peritoneal fluid (local infection) and blood; local synthesis of pyrogenic (IL-1 beta, IL-6) and antipyretic (IL-10) cytokines and central production of IL-6 and PGE(2), suggesting that these last are the central mediators of this response.

Augmented nitric oxide production and up-regulation of endothelial nitric oxide synthase during cecal ligation and perforation

Nitric oxide (NO) has been pointed out as being the main mediator involved in the hypotension and tissue injury taking place during sepsis. This study aimed to investigate the cellular mechanisms implicated in the acetylcholine (ACh)-induced relaxation detected in aortic rings isolated from rats submitted to cecal ligation and perforation (CLP group), 6 h post-CLP. The mean arterial pressure was recorded, and the concentration-effect curves for ACh were constructed for endothelium-intact aortic rings in the absence (control) or after incubation with one of the following NO synthase inhibitors: L-NAME (non-selective), L-NNA (more selective for eNOS), 7-nitroindazole (more selective for nNOS), or 1400W (selective for iNOS). The NO concentration was determined by using confocal microscopy. The protein expression of the NOS isoforms was quantified by Western blot analysis. The prostacyclin concentration was indirectly analyzed on the basis of 6-keto-prostaglandin F-1 alpha (6-keto-PGF(1 alpha)) levels measured by enzyme immunoassay. There were no differences between Sham- and CLP-operated rats in terms of the relaxation induced by acetylcholine. However, the NOS inhibitors reduced this relaxation in both groups, but this effect remained more pronounced in the CLP group as compared to the Sham group. The acetylcholine-induced NO production was higher in the rat aortic endothelial cells of the CLP group than in those of the Sham group. eNOS protein expression was larger in the CLP group, but the iNOS protein was not verified in any of the groups. The basal 6-keto-PGF(1 alpha) levels were higher in the CLP group, but the acetylcholine-stimulated levels did not increase in CLP as much as they did in the Sham group. Taken together, our results show that the augmented NO production in sepsis syndrome elicited by cecal ligation and perforation is due to eNOS up-regulation and not to iNOS. (C) 2012 Elsevier Inc. All rights reserved.

Impacto na epidemiologia da sepse tardia após a mudança do protocolo de antimicrobianos em uma UTIN de um serviço universitário

Advances in neonatology resulted in reducing the mortality rate and the consequent increase in survival of newborn pre terms (PTN). On the other hand, there was also a considerable increase in the risk of developing health care-related infection (HAI) in its most invasive, especially for bloodstream. This situation is worrying, and prevent the occurrence of it is a challenge and becomes one of the priorities in the Neonatal Intensive Care Unit (NICU). Sepsis is the main cause of death in critical neonates and affects more than one million newborns each year, representing 40% of all deaths in neonates. The incidence of late sepsis can reach 50% in NICUs. Currently the major responsible for the occurrence of sepsis in developed countries is the coagulase negative Staphylococcus (CoNS), followed by S. aureus. The cases of HAIs caused by resistant isolates for major classes of antimicrobial agents have been increasingly frequent in the NICU. Therefore, vancomycin has to be prescribed more frequently, and, today, the first option in the treatment of bloodstream infections by resistant Staphylococcus. The objectives of this study were to assess the impact on late sepsis in epidemiology III NICU after the change of the use of antimicrobials protocol; check the frequency of multiresistant microorganisms; assess the number of neonates who came to death. This study was conducted in NICU Level III HC-UFU. three study groups were formed based on the use of the proposed late sepsis treatment protocol, with 216 belonging to the period A, 207 B and 209 to the C. The work was divided into three stages: Period A: data collected from neonates admitted to the unit between September 2010 to August 2011. was using treatment of late sepsis: with oxacillin and gentamicin, oxacillin and amikacin, oxacillin and cefotaxime. Period B: data were collected from March 2012 to February 2013. Data collection was started six months after protocol change. Due to the higher prevalence of CoNS, the initial protocol was changed to vancomycin and cefotaxime. Period C: data were collected from newborns inteerne in the unit from September 2013 to August 2014. Data collection was started six months after the protocol change, which occurred in March 2013. From the 632 neonates included in this study, 511 (80,8%) came from the gynecology and obstetrics department of the HC-UFU. The mean gestational age was 33 weeks and the prevailing sex was male (55,7%). Seventy-nine percent of the studied neonates were hospitalized at the NICU HC-UFU III because of complications related to the respiratory system. Suspicion of sepsis took to hospitalization in the unit of 1,9% of newborns. In general, the infection rate was 34,5%, and the most frequent infectious sepsis syndrome 81,2%. There was a tendency to reduce the number of neonates who died between periods A 11 and C (p = 0,053). From the 176 cases of late sepsis, 73 were clinical sepsis and 103 had laboratory confirmation, with greater representation of Gram positive bacteria, which corresponded to 67.2% of the isolates and CoNS the most frequent micro-organism (91,5%). There was a statistically significant difference in the reduction of isolation of Gram positive microorganisms between periods A and C (p = 0,0365) as well as in reducing multidrug-resistant CoNS (A and B period p = 0,0462 and A and C period, p = 0,158). This study concluded that: the CoNS was the main microorganism responsible for the occurrence of late sepsis in neonates in the NICU of HC-UFU; the main risk factors for the occurrence of late sepsis were: birth weight <1500 g, use of PICC and CUV, need for mechanical ventilation and parenteral nutrition, SNAPPE> 24 and length of stay more than seven days; the new empirical treatment protocol late sepsis, based on the use of vancomycin associated cefepime, it was effective, since promoted a reduction in insulation CoNS blood cultures between the pre and post implementation of the Protocol (A and C, respectively); just as there was a reduction in the number of newborns who evolved to death between periods A and C.

A biomarker panel to discriminate between systemic inflammatory response syndrome and sepsis and sepsis severity

Introduction: In this study, we report on initial efforts to discover putative biomarkers for differential diagnosis of a systemic inflammatory response syndrome (SIRS) versus sepsis; and different stages of sepsis. In addition, we also investigated whether there are proteins that can discriminate between patients who survived sepsis from those who did not. Materials and Methods: Our study group consisted of 16 patients, of which 6 died and 10 survived. We daily measured 28 plasma proteins, for the whole stay of the patients in the ICU. Results: We observed that metalloproteinases and sE-selectin play a role in the distinction between SIRS and sepsis, and that IL-1, IP-10, sTNF-R2 and sFas appear to be indicative for the progression from sepsis to septic shock. A combined measurement of MMP-3, -10, IL-1, IP-10, sIL-2R, sFas, sTNF-R1, sRAGE, GM-CSF, IL-1 and Eotaxin allows for a good separation of patients that survived from those that died (mortality prediction with a sensitivity of 79% and specificity of 86%). Correlation analysis suggests a novel interaction between IL-1a and IP-10. Conclusion: The marker panel is ready to be verified in a validation study with or without therapeutic intervention.

Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis

The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. Patients older than 18 years admitted to the intensive care un

Aspirin as a potential treatment in sepsis or acute respiratory distress syndrome

Sepsis is a common condition that is associated with significant morbidity, mortality and health-care cost. Pulmonary and non-pulmonary sepsis are common causes of the acute respiratory distress syndrome (ARDS). The mortality from ARDS remains high despite protective lung ventilation, and currently there are no specific pharmacotherapies to treat sepsis or ARDS. Sepsis and ARDS are characterised by activation of the inflammatory cascade. Although there is much focus on the study of the dysregulated inflammation and its suppression, the associated activation of the haemostatic system has been largely ignored until recently. There has been extensive interest in the role that platelet activation can have in the inflammatory response through induction, aggregation and activation of leucocytes and other platelets. Aspirin can modulate multiple pathogenic mechanisms implicated in the development of multiple organ dysfunction in sepsis and ARDS. This review will discuss the role of the platelet, the mechanisms of action of aspirin in sepsis and ARDS, and aspirin as a potential therapy in treating sepsis and ARDS.

Fluid strategies and outcomes in patients with acute respiratory distress syndrome, systemic inflammatory response syndrome and sepsis: a protocol for a systematic review and meta-analysis

Background
Fluid administration to critically ill patients remains the subject of considerable controversy. While intravenous fluid given for resuscitation may be life-saving, a positive fluid balance over time is associated with worse outcomes in critical illness. The aim of this systematic review is to summarise the existing evidence regarding the relationship between fluid administration or balance and clinically important patient outcomes in critical illness.

Methods
We will search Medline, EMBASE, the Cochrane Central Register of Controlled Trials from 1980 to the present and key conference proceedings from 2009 to the present. We will include studies of critically ill adults and children with acute respiratory distress syndrome (ARDS), sepsis and systemic inflammatory response syndrome (SIRS). We will include randomised controlled trials comparing two or more fluid regimens of different volumes of fluid and observational studies reporting the relationship between volume of fluid administered or fluid balance and outcomes including mortality, lengths of intensive care unit and hospital stay and organ dysfunction. Two independent reviewers will assess articles for eligibility, data extraction and quality appraisal. We will conduct a narrative and/or meta-analysis as appropriate.

Discussion
While fluid management has been extensively studied and discussed in the critical care literature, no systematic review has attempted to summarise the evidence for post-resuscitation fluid strategies in critical illness. Results of the proposed systematic review will inform practice and the design of future clinical trials.

Systematic review registration
PROSPERO CRD42013005608. (http://​www.​crd.​york.​ac.​uk/​PROSPERO/​)

Enhanced expression of 70-kilodalton heat shock protein limits cell division in a sepsis-induced model of acute respiratory distress syndrome.

OBJECTIVE: Fibrotic changes are initiated early in acute respiratory distress syndrome. This may involve overproliferation of alveolar type II cells. In an animal model of acute respiratory distress syndrome, we have shown that the administration of an adenoviral vector overexpressing the 70-kd heat shock protein (AdHSP) limited pathophysiological changes. We hypothesized that this improvement may be modulated, in part, by an early AdHSP-induced attenuation of alveolar type II cell proliferation. DESIGN: Laboratory investigation. SETTING: Hadassah-Hebrew University and University of Pennsylvania animal laboratories. SUBJECTS: Sprague-Dawley Rats (250 g). INTERVENTIONS: Lung injury was induced in male Sprague-Dawley rats via cecal ligation and double puncture. At the time of cecal ligation and double puncture, we injected phosphate-buffered saline, AdHSP, or AdGFP (an adenoviral vector expressing the marker green fluorescent protein) into the trachea. Rats then received subcutaneous bromodeoxyuridine. In separate experiments, A549 cells were incubated with medium, AdHSP, or AdGFP. Some cells were also stimulated with tumor necrosis factor-alpha. After 48 hrs, cytosolic and nuclear proteins from rat lungs or cell cultures were isolated. These were subjected to immunoblotting, immunoprecipitation, electrophoretic mobility shift assay, fluorescent immunohistochemistry, and Northern blot analysis. MEASUREMENTS AND MAIN RESULTS: Alveolar type I cells were lost within 48 hrs of inducing acute respiratory distress syndrome. This was accompanied by alveolar type II cell proliferation. Treatment with AdHSP preserved alveolar type I cells and limited alveolar type II cell proliferation. Heat shock protein 70 prevented overexuberant cell division, in part, by inhibiting hyperphosphorylation of the regulatory retinoblastoma protein. This prevented retinoblastoma protein ubiquitination and degradation and, thus, stabilized the interaction of retinoblastoma protein with E2F1, a key cell division transcription factor. CONCLUSIONS: : Heat shock protein 70-induced attenuation of cell proliferation may be a useful strategy for limiting lung injury when treating acute respiratory distress syndrome if consistent in later time points.

The impact of body mass index on the development of systemic inflammatory response syndrome and sepsis in patients with polytrauma

PURPOSE: Obesity is a growing problem in industrial nations. Our aim was to examine how overweight patients coped with systemic inflammatory response syndrome (SIRS) after polytrauma. METHODS: A total of 651 patients were included in this retrospective study, with an ISS≥16 and age≥16 years. The sample was subdivided into three groups: body mass index (BMI; all in kg/m(2))<25, BMI 25-30 and BMI>30, or low, intermediate and high BMI. The SIRS score was measured over 31 days after admission together with measurements of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT). Data are given as the mean±SEM if not otherwise indicated. Kruskal-Wallis and χ(2) tests were used for statistical analysis and the significance level was set at p<.05. RESULTS: The maximum SIRS score was reached in the low BMI-group at 3.4±0.4, vs. 2.3±0.1 and 2.5±0.2 in the intermediate BMI-group and high BMI-group, respectively (p<.0001). However, the maximum SIRS score was reached earlier in the BMI 25-30 group at 1.8±0.2 days, vs. 3.4±0.4 and 2.5±0.2 days in the BMI<25 and BMI>30 groups, respectively (p<.0001). The incidence of sepsis was significantly higher in the low BMI group at 46.1%, vs. 0.2% and 0% in the BMI 25-30 and BMI>30 groups, respectively (p<.0001). No significant differences in the CRP, IL-6 or PCT levels were found between groups. CONCLUSIONS: A higher BMI seemed to be protective for these patients with polytrauma-associated inflammatory problems.

Mesenteric lymphangitis and sepsis due to RTX toxin-producing Actinobacillus spp in 2 foals with hypothyroidism-dysmaturity syndrome

Actinobacillus suis-like organisms (ASLOs) have been isolated from the genital, respiratory, and digestive tracts of healthy adult horses, horses with respiratory disease, and septic foals. Two foals with congenital hypothyroidism-dysmaturity syndrome from separate farms developed ASLO infection. At necropsy, both had contracted carpal flexor tendons, thyroid hyperplasia, and thrombotic and necrotizing mesenteric lymphangitis and lymphadenitis; one foal also had mandibular prognathism. Numerous ASLOs were isolated from tissues from both foals, including intestine. Biochemical testing and mass spectrometric analysis of the two Actinobacillus isolates did not allow unequivocal identification. Comparative genetic analysis was done on these and similar isolates, including phylogeny based on 16S rRNA, rpoB and recN genes, as well as RTX (repeat in toxin) toxin typing of apxIA-apxIVA and aqxA genes. One isolate was identified as Actinobacillus suis sensu stricto, based on the presence of apxIA and apxIIA but not aqxA, whereas the other isolate had aqxA but neither apxIA nor apxIIA, consistent with A equuli ssp haemolyticus. Based on genotypic analysis of the isolates included for comparison, 3 of 3 equine ASLOs and 2 of 5 A equuli isolates were reclassified as A equuli subsp haemolyticus, emphasizing the importance of toxin genotyping in accurate classification of actinobacilli.

Temporal trends in the systemic inflammatory response syndrome, sepsis, and medical coding of sepsis.

BACKGROUND Recent reports using administrative claims data suggest the incidence of community- and hospital-onset sepsis is increasing. Whether this reflects changing epidemiology, more effective diagnostic methods, or changes in physician documentation and medical coding practices is unclear. METHODS We performed a temporal-trend study from 2008 to 2012 using administrative claims data and patient-level clinical data of adult patients admitted to Barnes-Jewish Hospital in St. Louis, Missouri. Temporal-trend and annual percent change were estimated using regression models with autoregressive integrated moving average errors. RESULTS We analyzed 62,261 inpatient admissions during the 5-year study period. 'Any SIRS' (i.e., SIRS on a single calendar day during the hospitalization) and 'multi-day SIRS' (i.e., SIRS on 3 or more calendar days), which both use patient-level data, and medical coding for sepsis (i.e., ICD-9-CM discharge diagnosis codes 995.91, 995.92, or 785.52) were present in 35.3 %, 17.3 %, and 3.3 % of admissions, respectively. The incidence of admissions coded for sepsis increased 9.7 % (95 % CI: 6.1, 13.4) per year, while the patient data-defined events of 'any SIRS' decreased by 1.8 % (95 % CI: -3.2, -0.5) and 'multi-day SIRS' did not change significantly over the study period. Clinically-defined sepsis (defined as SIRS plus bacteremia) and severe sepsis (defined as SIRS plus hypotension and bacteremia) decreased at statistically significant rates of 5.7 % (95 % CI: -9.0, -2.4) and 8.6 % (95 % CI: -4.4, -12.6) annually. All-cause mortality, SIRS mortality, and SIRS and clinically-defined sepsis case fatality did not change significantly during the study period. Sepsis mortality, based on ICD-9-CM codes, however, increased by 8.8 % (95 % CI: 1.9, 16.2) annually. CONCLUSIONS The incidence of sepsis, defined by ICD-9-CM codes, and sepsis mortality increased steadily without a concomitant increase in SIRS or clinically-defined sepsis. Our results highlight the need to develop strategies to integrate clinical patient-level data with administrative data to draw more accurate conclusions about the epidemiology of sepsis.