12 research outputs found
Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study
Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis
Plasma lipid profiles discriminate bacterial from viral infection in febrile children
Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection are often non-specific, and there is no definitive test for the accurate diagnosis of infection. The 'omics' approaches to identifying biomarkers from the host-response to bacterial infection are promising. In this study, lipidomic analysis was carried out with plasma samples obtained from febrile children with confirmed bacterial infection (n = 20) and confirmed viral infection (n = 20). We show for the first time that bacterial and viral infection produces distinct profile in the host lipidome. Some species of glycerophosphoinositol, sphingomyelin, lysophosphatidylcholine and cholesterol sulfate were higher in the confirmed virus infected group, while some species of fatty acids, glycerophosphocholine, glycerophosphoserine, lactosylceramide and bilirubin were lower in the confirmed virus infected group when compared with confirmed bacterial infected group. A combination of three lipids achieved an area under the receiver operating characteristic (ROC) curve of 0.911 (95% CI 0.81 to 0.98). This pilot study demonstrates the potential of metabolic biomarkers to assist clinicians in distinguishing bacterial from viral infection in febrile children, to facilitate effective clinical management and to the limit inappropriate use of antibiotics
Site variability in regulatory oversight for an international study of pediatric sepsis
Objectives: Duplicative institutional review board/research ethics committee review for multicenter studies may impose administrative burdens and inefficiencies affecting study implementation and quality. Understanding variability in site-specific institutional review board/research ethics committee assessment and barriers to using a single review committee (an increasingly proposed solution) can inform a more efficient process. We provide needed data about the regulatory oversight process for the Sepsis PRevalence, OUtcomes, and Therapies multicenter point prevalence study. Design: Survey. Setting: Sites invited to participate in Sepsis PRevalence, OUtcomes, and Therapies. Subjects: Investigators at sites that expressed interest and/or participated in Sepsis PRevalence, OUtcomes, and Therapies. Interventions: None. Measurements and Main Results: Using an electronic survey, we collected data about 1) logistics of protocol submission, 2) institutional review board/research ethics committee requested modifications, and 3) use of a single institutional review board (for U.S. sites). We collected surveys from 104 of 167 sites (62%). Of the 97 sites that submitted the protocol for institutional review board/research ethics committee review, 34% conducted full board review, 54% expedited review, and 4% considered the study exempt. Time to institutional review board/research ethics committee approval required a median of 34 (range 3-186) days, which took longer at sites that required protocol modifications (median [interquartile range] 50 d [35-131 d] vs 32 d [14-54 d)]; p = 0.02). Enrollment was delayed at eight sites due to prolonged (> 50 d) time to approval. Of 49 U.S. sites, 43% considered using a single institutional review board, but only 18% utilized this option. Time to final approval for U.S. sites using the single institutional review board was 62 days (interquartile range, 34-70 d) compared with 34 days (interquartile range, 15-54 d) for nonsingle institutional review board sites (p = 0.16). Conclusions: Variability in regulatory oversight was evident for this minimal-risk observational research study, most notably in the category of type of review conducted. Duplicative review prolonged time to protocol approval at some sites. Use of a single institutional review board for U.S. sites was rare and did not improve efficiency of protocol approval. Suggestions for minimizing these challenges are provided
Acute Kidney Injury in Pediatric Severe Sepsis: An Independent Risk Factor for Death and New Disability
Objectives: The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Design: Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. Setting: One hundred twenty-eight PICUs in 26 countries. Patients: Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p < 0.001). Severe acute kidney injury was independently associated with death or new moderate disability (adjusted odds ratio, 2.5; 95% CI, 1.5-4.2; p = 0.001) after adjustment for age, region, baseline disability, malignancy, invasive mechanical ventilation, albumin administration, and the pediatric logistic organ dysfunction score. Conclusions: In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability
Acute kidney injury in pediatric severe sepsis : An independent risk factor for death and new disability
Objectives: The prevalence of septic acute kidney injury and impact on functional status of PICU survivors are unknown. We used data from an international prospective severe sepsis study to elucidate functional outcomes of children suffering septic acute kidney injury. Design: Secondary analysis of patients in the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study: acute kidney injury was defined on the study day using Kidney Disease Improving Global Outcomes definitions. Patients with no acute kidney injury or stage 1 acute kidney injury ("no/mild acute kidney injury") were compared with those with stage 2 or 3 acute kidney injury ("severe acute kidney injury"). The primary outcome was a composite of death or new moderate disability at discharge defined as a Pediatric Overall Performance Category score of 3 or higher and increased by 1 from baseline. Setting: One hundred twenty-eight PICUs in 26 countries. Patients: Children with severe sepsis in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: One hundred two (21%) of 493 patients had severe acute kidney injury. More than twice as many patients with severe acute kidney injury died or developed new moderate disability compared with those with no/mild acute kidney injury (64% vs 30%; p Conclusions: In a multinational cohort of critically ill children with severe sepsis and high mortality rates, septic acute kidney injury is independently associated with further increased death or new disability.</p
High Levels of Morbidity and Mortality among Pediatric Hematopoietic Cell Transplant Recipients with Severe Sepsis: Insights from the Sepsis PRevalence, OUtcomes, and Therapies International Point Prevalence Study
Objectives: Pediatric severe sepsis is a major cause of morbidity and mortality worldwide, and hematopoietic cell transplant patients represent a high-risk population. We assessed the epidemiology of severe sepsis in hematopoietic cell transplant patients, describing patient outcomes compared with children with no history of hematopoietic cell transplant. Design: Secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies point prevalence study, comparing demographics, sepsis etiology, illness severity, organ dysfunction, and sepsis-related treatments in patients with and without hematopoietic cell transplant. The primary outcome was hospital mortality. Multivariable logistic regression models were used to determine adjusted differences in mortality. Setting: International; 128 PICUs in 26 countries. Patients: Pediatric patients with severe sepsis prospectively identified over a 1-year period. Interventions: None. Measurements and Main Results: In patients with severe sepsis, 37/567 (6.5%) had a history of hematopoietic cell transplant. Compared with patients without hematopoietic cell transplant, hematopoietic cell transplant patients had significantly higher hospital mortality (68% vs 23%; p < 0.001). Hematopoietic cell transplant patients were more likely to have hospital acquired sepsis and had more preexisting renal and hepatic dysfunction than non-hematopoietic cell transplant patients with severe sepsis. History of hematopoietic cell transplant, renal replacement therapy, admission from inpatient floor, and number of organ dysfunctions at severe sepsis recognition were independently associated with hospital mortality in multivariable analysis; hematopoietic cell transplant conferred the highest odds of mortality (odds ratio, 4.00; 95% CI, 1.78-8.98). In secondary analysis of hematopoietic cell transplant patients compared with other immunocompromised patients with severe sepsis, history of hematopoietic cell transplant remained independently associated with hospital mortality (odds ratio, 3.03; 95% CI, 1.11-8.27). Conclusions: In an international study of pediatric severe sepsis, history of hematopoietic cell transplant is associated with a four-fold increased odds of hospital mortality after adjustment for potential measured confounders. Hematopoietic cell transplant patients more often originated from within the hospital compared to children with severe sepsis without hematopoietic cell transplant, possibly providing an earlier opportunity for sepsis recognition and intervention in this high-risk population
Comparison of Pediatric Severe Sepsis Managed in U.S. and European ICUs
Copyright © 2016 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.Objectives: Pediatric severe sepsis remains a significant global health problem without new therapies despite many multicenter clinical trials. We compared children managed with severe sepsis in European and U.S. PICUs to identify geographic variation, which may improve the design of future international studies. Design: We conducted a secondary analysis of the Sepsis PRevalence, OUtcomes, and Therapies study. Data about PICU characteristics, patient demographics, therapies, and outcomes were compared. Multivariable regression models were used to determine adjusted differences in morbidity and mortality. Setting: European and U.S. PICUs. Patients: Children with severe sepsis managed in European and U.S. PICUs enrolled in the Sepsis PRevalence, OUtcomes, and Therapies study. Interventions: None. Measurements and Main Results: European PICUs had fewer beds (median, 11 vs 24; p < 0.001). European patients were younger (median, 1 vs 6 yr; p < 0.001), had higher severity of illness (median Pediatric Index of Mortality-3, 5.0 vs 3.8; p = 0.02), and were more often admitted from the ward (37% vs 24%). Invasive mechanical ventilation, central venous access, and vasoactive infusions were used more frequently in European patients (85% vs 68%, p = 0.002; 91% vs 82%, p = 0.05; and 71% vs 50%; p < 0.001, respectively). Raw morbidity and mortality outcomes were worse for European compared with U.S. patients, but after adjusting for patient characteristics, there were no significant differences in mortality, multiple organ dysfunction, disability at discharge, length of stay, or ventilator/vasoactive-free days. Conclusions: Children with severe sepsis admitted to European PICUs have higher severity of illness, are more likely to be admitted from hospital wards, and receive more intensive care therapies than in the United States. The lack of significant differences in morbidity and mortality after adjusting for patient characteristics suggests that the approach to care between regions, perhaps related to PICU bed availability, needs to be considered in the design of future international clinical trials in pediatric severe sepsis
Risk Factors for Mortality in Pediatric Postsurgical versus Medical Severe Sepsis
Background: Sepsis is a leading cause of morbidity and mortality after surgery. Most studies
regarding sepsis do not differentiate between patients who have had recent surgery and
those without. Few data exist regarding the risk factors for poor outcomes in pediatric
postsurgical sepsis. Our hypothesis is pediatric postsurgical, and medical patients with
severe sepsis have unique risk factors for mortality.
Methods: Data were extracted from a secondary analysis of an international point preva-
lence study of pediatric severe sepsis. Sites included 128 pediatric intensive care units from
26 countries. Pediatric patients with severe sepsis were categorized into those who had
recent surgery (postsurgical sepsis) versus those that did not (medical sepsis) before sepsis
onset. Multivariable logistic regression models were used to determine risk factors for
mortality.
Results: A total of 556 patients were included: 138 with postsurgical and 418 with medical
sepsis. In postsurgical sepsis, older age, admission from the hospital ward, multiple organ
dysfunction syndrome at sepsis recognition, and cardiovascular and respiratory comor-
bidities were independent risk factors for death. In medical sepsis, resource-limited region,
hospital-acquired infection, multiple organ dysfunction syndrome at sepsis recognition,
higher Pediatric Index of Mortality-3 score, and malignancy were independent risk factors
for death.
Conclusions: Pediatric patients with postsurgical sepsis had different risk factors for mor-
tality compared with medical sepsis. This included a higher mortality risk in postsurgical
patients presenting to the intensive care unit from the hospital ward. These data suggest
an opportunity to develop and test early warning systems specific to pediatric sepsis in the
postsurgical population
New or Progressive Multiple Organ Dysfunction Syndrome in Pediatric Severe Sepsis: A Sepsis Phenotype With Higher Morbidity and Mortality
Objectives: To describe the epidemiology, morbidity, and mortality of new or progressive multiple organ dysfunction syndrome in children with severe sepsis. Design: Secondary analysis of a prospective, cross-sectional, point prevalence study. Setting: International, multicenter PICUs. Patients: Pediatric patients with severe sepsis identified on five separate days over a 1-year period. Interventions: None. Measurements and Main Results: Of 567 patients from 128 PICUs in 26 countries enrolled, 384 (68%) developed multiple organ dysfunction syndrome within 7 days of severe sepsis recognition. Three hundred twenty-seven had multiple organ dysfunction syndrome on the day of sepsis recognition. Ninety-one of these patients developed progressive multiple organ dysfunction syndrome, whereas an additional 57 patients subsequently developed new multiple organ dysfunction syndrome, yielding a total proportion with severe sepsis-associated new or progressive multiple organ dysfunction syndrome of 26%. Hospital mortality in patients with progressive multiple organ dysfunction syndrome was 51% compared with patients with new multiple organ dysfunction syndrome (28%) and those with single-organ dysfunction without multiple organ dysfunction syndrome (10%) (p < 0.001). Survivors of new or progressive multiple organ dysfunction syndrome also had a higher frequency of moderate to severe disability defined as a Pediatric Overall Performance Category score of greater than or equal to 3 and an increase of greater than or equal to 1 from baseline: 22% versus 29% versus 11% for progressive, new, and no multiple organ dysfunction syndrome, respectively (p < 0.001). Conclusions: Development of new or progressive multiple organ dysfunction syndrome is common (26%) in severe sepsis and is associated with a higher risk of morbidity and mortality than severe sepsis without new or progressive multiple organ dysfunction syndrome. Our data support the use of new or progressive multiple organ dysfunction syndrome as an important outcome in trials of pediatric severe sepsis although efforts are needed to validate whether reducing new or progressive multiple organ dysfunction syndrome leads to improvements in more definitive morbidity and mortality endpoints
Recommended from our members
Paediatric acute respiratory distress syndrome incidence and epidemiology (PARDIE): an international, observational study
BackgroundPaediatric acute respiratory distress syndrome (PARDS) is associated with high mortality in children, but until recently no paediatric-specific diagnostic criteria existed. The Pediatric Acute Lung Injury Consensus Conference (PALICC) definition was developed to overcome limitations of the Berlin definition, which was designed and validated for adults. We aimed to determine the incidence and outcomes of children who meet the PALICC definition of PARDS.MethodsIn this international, prospective, cross-sectional, observational study, 145 paediatric intensive care units (PICUs) from 27 countries were recruited, and over a continuous 5 day period across 10 weeks all patients were screened for enrolment. Patients were included if they had a new diagnosis of PARDS that met PALICC criteria during the study week. Exclusion criteria included meeting PARDS criteria more than 24 h before screening, cyanotic heart disease, active perinatal lung disease, and preparation or recovery from a cardiac intervention. Data were collected on the PICU characteristics, patient demographics, and elements of PARDS (ie, PARDS risk factors, hypoxaemia severity metrics, type of ventilation), comorbidities, chest imaging, arterial blood gas measurements, and pulse oximetry. The primary outcome was PICU mortality. Secondary outcomes included 90 day mortality, duration of invasive mechanical and non-invasive ventilation, and cause of death.FindingsBetween May 9, 2016, and June 16, 2017, during the 10 study weeks, 23 280 patients were admitted to participating PICUs, of whom 744 (3·2%) were identified as having PARDS. 95% (708 of 744) of patients had complete data for analysis, with 17% (121 of 708; 95% CI 14-20) mortality, whereas only 32% (230 of 708) of patients met Berlin criteria with 27% (61 of 230) mortality. Based on hypoxaemia severity at PARDS diagnosis, mortality was similar among those who were non-invasively ventilated and with mild or moderate PARDS (10-15%), but higher for those with severe PARDS (33% [54 of 165; 95% CI 26-41]). 50% (80 of 160) of non-invasively ventilated patients with PARDS were subsequently intubated, with 25% (20 of 80; 95% CI 16-36) mortality. By use of PALICC PARDS definition, severity of PARDS at 6 h after initial diagnosis (area under the curve [AUC] 0·69, 95% CI 0·62-0·76) discriminates PICU mortality better than severity at PARDS diagnosis (AUC 0·64, 0·58-0·71), and outperforms Berlin severity groups at 6 h (0·64, 0·58-0·70; p=0·01).InterpretationThe PALICC definition identified more children as having PARDS than the Berlin definition, and PALICC PARDS severity groupings improved the stratification of mortality risk, particularly when applied 6 h after PARDS diagnosis. The PALICC PARDS framework should be considered for use in future epidemiological and therapeutic research among children with PARDS.FundingUniversity of Southern California Clinical Translational Science Institute, Sainte Justine Children's Hospital, University of Montreal, Canada, Réseau en Santé Respiratoire du Fonds de Recherche Quebec-Santé, and Children's Hospital Los Angeles, Department of Anesthesiology and Critical Care Medicine