Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Weiss et al. Critical Care (2015) 19:325 DOI 10.1186/s13054-015-1055-x RESEARCH Open Access Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study Scott L. Weiss1*, Julie C. Fitzgerald1, Frank A. Maffei2, Jason M. Kane3, Antonio Rodriguez-Nunez4, Deyin D. Hsing5, Deborah Franzon6, Sze Ying Kee7, Jenny L. Bush1, Jason A. Roy8, Neal J. Thomas9, and Vinay M. Nadkarni1, for the SPROUT Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network Abstract 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 κ. 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 (κ ± 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. * Correspondence: 1 Division of Critical Care Medicine, Department of Anesthesia and Critical Care, The Children’s Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA Full list of author information is available at the end of the article © 2015 Weiss et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Weiss et al. Critical Care (2015) 19:325 Introduction Sepsis is a leading cause of death in children worldwide, responsible for an estimated 75,000 hospitalizations annually in the United States and nearly 50 % of all childhood hospital deaths worldwide [1–5]. Within the spectrum of this syndrome, severe sepsis refers to children with shock or other organ dysfunction and is the high-risk group targeted for interventional studies in the pediatric intensive care unit (PICU) [6]. Investigators in clinical trials of severe sepsis face important challenges that have contributed to high failure rates for many promising novel therapies, with few attempts to include children [7]. One fundamental issue is that the sepsis syndrome is characterized by non-specific physiologic abnormalities that encompass a heterogeneous population. Consensus criteria for pediatric sepsis were therefore established to facilitate consistent enrollment across research studies [6]. Many of these criteria have since been adopted for use in clinical practice [8]; however, published reports have demonstrated only moderate overlap of physician diagnosis of severe sepsis with consensus criteria [9, 10]. These findings raise concern that many children diagnosed and treated for severe sepsis in clinical practice may have important physiologic—and outcome—differences from those studied in interventional trials [9, 10]. The degree to which a study population is representative of patients diagnosed and treated in clinical practice has a major impact on the external validity of a study [11–13]. Although physician diagnosis serves clinical practice and consensus criteria were intended primarily for research, the alignment of these two methods to identify children with severe sepsis will significantly impact the extent to which study results translate into effective care at the bedside. Moreover, criteria that purposely define a disorder as a decompensated state at one extreme of the entire spectrum—as the existing pediatric consensus definitions currently do for severe sepsis and septic shock—may hinder early clinical diagnosis or delay enrollment in a clinical trial. Although the inherent challenge between research efficacy and clinical effectiveness is not limited to sepsis [14–17], understanding the extent to which consensus criteria for pediatric severe sepsis are in agreement with clinical practice will help to improve understanding of the utility of these criteria and to identify ways to improve both physician diagnosis and consensus definitions. To date, the agreement of physician diagnosis with consensus criteria for pediatric severe sepsis has not been evaluated in a large-scale setting. The Sepsis PRevalence, OUtcomes, and Therapies (SPROUT) study researchers screened nearly 7000 PICU patients for severe sepsis at 128 sites across 26 countries using consensus criteria [18]. In addition, the attending Page 2 of 10 physician caring for each patient provided an independent diagnosti (...truncated)