Update on pediatric sepsis: a review

Kawasaki Journal of Intensive Care (2017) 5:47 DOI 10.1186/s40560-017-0240-1 REVIEW Open Access Update on pediatric sepsis: a review Tatsuya Kawasaki Abstract Background: Sepsis is one of the leading causes of mortality among children worldwide. Unfortunately, however, reliable evidence was insufficient in pediatric sepsis and many aspects in clinical practice actually depend on expert consensus and some evidence in adult sepsis. More recent findings have given us deep insights into pediatric sepsis since the publication of the Surviving Sepsis Campaign guidelines 2012. Main text: New knowledge was added regarding the hemodynamic management and the timely use of antimicrobials. Quality improvement initiatives of pediatric “sepsis bundles” were reported to be successful in clinical outcomes by several centers. Moreover, a recently published global epidemiologic study (the SPROUT study) did not only reveal the demographics, therapeutic interventions, and prognostic outcomes but also elucidated the inappropriateness of the current definition of pediatric sepsis. Conclusions: With these updated knowledge, the management of pediatric sepsis would be expected to make further progress. In addition, it is meaningful that the fundamental data on which future research should be based were established through the SPROUT study. Keywords: Sepsis, Septic shock, Pediatric, Child, Epidemiology, Surviving Sepsis Campaign, Antibiotics, Hemodynamic management, Algorithm, Prognosis Background Sepsis is a life-threatening condition which affects many children regardless of some underlying healthcare issues [1]. Sepsis is said to be one of the leading causes of death among children even in advanced countries. Although demographic data does not clearly show it, many children who are reported to die from other underlying conditions actually die directly from sepsis. The management of pediatric sepsis was comprehensively advocated through systematic review process in the Surviving Sepsis Campaign guidelines (SSCG) 2008 [2] and 2012 [3]. Unfortunately, however, many recommendations and suggestions were still based on low quality evidence and expert consensus, and sometimes only on evidence in adult sepsis. Furthermore, the latest version of SSCG did not include a specific description of the management of pediatric sepsis [4]. This review mainly focuses on updated knowledge and hot topics regarding pediatric sepsis published after the SSCG 2012 [3]. Correspondence: Department of Pediatric Critical Care, Shizuoka Children’s Hospital, 860 Ursuhiyama, Aoi-ku, Shizuoka, Shizuoka 420-8660, Japan Definition of pediatric sepsis For the past two decades, sepsis has been defined as “systemic inflammatory response syndrome (SIRS) caused by infection” both for adults and children [5–7]. This definition, however, has long been criticized for its too broad inclusion of milder conditions, such as influenza virus infection without any organ dysfunction. In fact, Churpek et al. revealed that nearly half of the adult patients admitted to the hospital wards fulfilled two or more SIRS criteria at least once during their ward stay [8], while Kaukonen et al. showed that about 12% of the adult ICU patients with some infection and at least one organ dysfunction were negative for the SIRS criteria but that their mortality rate was still substantial [9]. These findings imply that the SIRS criteria are not an appropriate tool to screen at-risk patients and that the severity of organ dysfunctions may be able to substitute for SIRS to identify patients with higher mortality risk. Taking these issues into consideration, new sepsis criteria were advocated as “Sepsis-3” in 2017, which redefined sepsis as infection complicated by one or more organ dysfunctions [10]. Organ system dysfunctions are assessed with an increase in the Sequential Organ Failure Assessment (SOFA) score by 2 or more points. The © The Author(s). 2017 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. Kawasaki Journal of Intensive Care (2017) 5:47 main purpose of this transition is to focus on more severe patients for the recruitment in future intervention studies [10]. Unfortunately, this change in the definition of sepsis is only applied to adult population at this moment [10]. When it comes to the consensus definition in children [7], other issues have been pointed out in addition to similar criticism to the adult definition, especially regarding the pediatric SIRS and organ dysfunction criteria. The threshold of tachypnea in the pediatric SIRS criteria, for example, overlaps even the normal range for adults (e.g., 18 breaths/min for 6–12-year-old children and 14 for 13–18-year-old adolescents) [7]. The standardized criteria for each organ dysfunction [7] are not based on evidence related to clinical outcomes. Moreover, a couple of studies revealed only the moderate level of agreement, approximately two thirds, in the diagnosis of severe sepsis between physician’s clinical judgment and consensus criteria [11–13], which obviously suggests that the current consensus criteria of pediatric sepsis based on the concept of SIRS do not play an effective role in identifying clinically hazardous patients. It is strongly desirable that pediatric sepsis should be redefined on the basis of organ dysfunction scoring in accordance with the adult Sepsis-3 in near future [13, 14]. Epidemiology The epidemiology of pediatric sepsis varies from study to study probably because of their different era, population, and diagnostic criteria. Watson et al. first reported the population-based incidence and outcomes of severe sepsis among children under 19 years old in seven states in the USA in 1995 [1]. The incidence was 0.56 cases per 1000 children per year, which was highest among infants (5.16 per 1000) and fell dramatically with age (0.20 per 1000 among 10–14-year-olds). Their hospital mortality was 10.3%, which varied little with age and was higher among children with some co-morbidity. More recently, a couple of studies from the USA added new findings. Following up the same population as Watson’s study [1], Hartman et al. reported that the prevalence was steadily increasing from 1995 to 2005 by 81%, which reached 0.89 cases per 1000 children in 2005 [15]. The case-fatality rate, on the other hand, dropped from 10.3% to 8.9% for that decade [15]. Based on the hospitalization database from the 44 children’s hospitals in the USA, Balamut (...truncated)