Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis
- Wendy J Pomerantz, MD, MS
Wendy J Pomerantz, MD, MS
- Co-Director, Injury Free Coalition of Greater Cincinnati
- Professor of Clinical Pediatrics
- Cincinnati Children's Hospital Medical Center
- Scott L Weiss, MD
Scott L Weiss, MD
- Assistant Professor of Anesthesiology, Critical Care, and Pediatrics
- The Children’s Hospital of Philadelphia, University of Pennsylvania
- Section Editors
- Susan B Torrey, MD
Susan B Torrey, MD
- Section Editor — Pediatric Resuscitation; Pediatric Trauma
- Director, Division of Pediatric Emergency Medicine
- Associate Professor of Emergency Medicine and Pediatrics (Clinical)
- NYU School of Medicine
- Sheldon L Kaplan, MD
Sheldon L Kaplan, MD
- Editor-in-Chief — Pediatrics
- Section Editor — Pediatric Infectious Diseases
- Professor and Vice Chairman for Clinical Affairs
- Baylor College of Medicine
- Adrienne G Randolph, MD, MSc
Adrienne G Randolph, MD, MSc
- Section Editor — Pediatric Critical Care Medicine
- Professor of Anaesthesia and Pediatrics
- Harvard Medical School
- Deputy Editor
- James F Wiley, II, MD, MPH
James F Wiley, II, MD, MPH
- Senior Deputy Editor — Adult and Pediatric Emergency Medicine
- Senior Deputy Editor — Primary Care Sports Medicine (Adolescents and Adults)
- Professor of Pediatrics and Emergency Medicine/Traumatology
- University of Connecticut School of Medicine
Sepsis is a clinical syndrome that complicates severe infection and is characterized by the systemic inflammatory response syndrome (SIRS), immune dysregulation, microcirculatory derangements, and end-organ dysfunction. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability, and leukocyte accumulation.
Although inflammation is an essential host response, the onset and progression of sepsis center upon a "dysregulation" of the normal response, usually with an increase in both proinflammatory and antiinflammatory mediators, initiating a chain of events that leads to widespread tissue injury. Evidence supports a state of acquired immune suppression or immunoparalysis in some patients, which may occur simultaneously with or following the initial proinflammatory response [1,2]. It is this dysregulated host response rather than the primary infectious microorganism that is typically responsible for multiple organ failure and adverse outcomes in sepsis. (See "Pathophysiology of sepsis".)
Early recognition of sepsis is crucial to ensuring the best outcomes in children and is aided by a working knowledge of the children at particular risk, the common pathogens, and the clinical manifestations. The definition, epidemiology, clinical manifestations, and diagnosis of the systematic inflammatory response syndrome and sepsis in children are discussed here.
The rapid recognition, resuscitation, and initial management of pediatric septic shock and the evaluation and management of undifferentiated shock in children are discussed separately:
- Hotchkiss RS, Karl IE. The pathophysiology and treatment of sepsis. N Engl J Med 2003; 348:138.
- Hall MW, Knatz NL, Vetterly C, et al. Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome. Intensive Care Med 2011; 37:525.
- Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6:2.
- Brierley J, Carcillo JA, Choong K, et al. Clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 2009; 37:666.
- Weiss SL, Parker B, Bullock ME, et al. Defining pediatric sepsis by different criteria: discrepancies in populations and implications for clinical practice. Pediatr Crit Care Med 2012; 13:e219.
- Pavare J, Grope I, Gardovska D. Prevalence of systemic inflammatory response syndrome (SIRS) in hospitalized children: a point prevalence study. BMC Pediatr 2009; 9:25.
- Juskewitch JE, Prasad S, Salas CF, Huskins WC. Reliability of the identification of the systemic inflammatory response syndrome in critically ill infants and children. Pediatr Crit Care Med 2012; 13:e55.
- Paul R, Melendez E, Stack A, et al. Improving adherence to PALS septic shock guidelines. Pediatrics 2014; 133:e1358.
- Nakagawa S, Shime N. Respiratory rate criteria for pediatric systematic inflammatory response syndrome. Pediatr Crit Care Med 2014; 15:182.
- Levy MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference. Intensive Care Med 2003; 29:530.
- Wilkinson JD, Pollack MM, Glass NL, et al. Mortality associated with multiple organ system failure and sepsis in pediatric intensive care unit. J Pediatr 1987; 111:324.
- Leteurtre S, Martinot A, Duhamel A, et al. Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study. Lancet 2003; 362:192.
- Graciano AL, Balko JA, Rahn DS, et al. The Pediatric Multiple Organ Dysfunction Score (P-MODS): development and validation of an objective scale to measure the severity of multiple organ dysfunction in critically ill children. Crit Care Med 2005; 33:1484.
- Weiss SL, Fitzgerald JC, Pappachan J, et al. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med 2015; 191:1147.
- Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS. Trends in the epidemiology of pediatric severe sepsis*. Pediatr Crit Care Med 2013; 14:686.
- Ruth A, McCracken CE, Fortenberry JD, et al. Pediatric severe sepsis: current trends and outcomes from the Pediatric Health Information Systems database. Pediatr Crit Care Med 2014; 15:828.
- Balamuth F, Weiss SL, Neuman MI, et al. Pediatric severe sepsis in U.S. children's hospitals. Pediatr Crit Care Med 2014; 15:798.
- Wang Y, Sun B, Yue H, et al. An epidemiologic survey of pediatric sepsis in regional hospitals in China. Pediatr Crit Care Med 2014; 15:814.
- Children: reducing mortality. World Health Organization, September 2014. www.who.int/mediacentre/factsheets/fs178/en/.
- Watson RS, Carcillo JA, Linde-Zwirble WT, et al. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med 2003; 167:695.
- Odetola FO, Gebremariam A, Freed GL. Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis. Pediatrics 2007; 119:487.
- Kutko MC, Calarco MP, Flaherty MB, et al. Mortality rates in pediatric septic shock with and without multiple organ system failure. Pediatr Crit Care Med 2003; 4:333.
- Jaramillo-Bustamante JC, Marín-Agudelo A, Fernández-Laverde M, Bareño-Silva J. Epidemiology of sepsis in pediatric intensive care units: first Colombian multicenter study. Pediatr Crit Care Med 2012; 13:501.
- Han YY, Carcillo JA, Dragotta MA, et al. Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics 2003; 112:793.
- Butt W. Septic shock. Pediatr Clin North Am 2001; 48:601.
- Gaines NN, Patel B, Williams EA, Cruz AT. Etiologies of septic shock in a pediatric emergency department population. Pediatr Infect Dis J 2012; 31:1203.
- Nadel S, Goldstein B, Williams MD, et al. Drotrecogin alfa (activated) in children with severe sepsis: a multicentre phase III randomised controlled trial. Lancet 2007; 369:836.
- Hussain FM, Boyle-Vavra S, Bethel CD, Daum RS. Current trends in community-acquired methicillin-resistant Staphylococcus aureus at a tertiary care pediatric facility. Pediatr Infect Dis J 2000; 19:1163.
- Yogaraj JS, Elward AM, Fraser VJ. Rate, risk factors, and outcomes of nosocomial primary bloodstream infection in pediatric intensive care unit patients. Pediatrics 2002; 110:481.
- Lee CY, Chen PY, Huang FL, Lin CF. Microbiologic spectrum and susceptibility pattern of clinical isolates from the pediatric intensive care unit in a single medical center - 6 years' experience. J Microbiol Immunol Infect 2009; 42:160.
- Jones RN. Resistance patterns among nosocomial pathogens: trends over the past few years. Chest 2001; 119:397S.
- National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control 2004; 32:470.
- Zaoutis TE, Prasad PA, Localio AR, et al. Risk factors and predictors for candidemia in pediatric intensive care unit patients: implications for prevention. Clin Infect Dis 2010; 51:e38.
- Lucignano B, Ranno S, Liesenfeld O, et al. Multiplex PCR allows rapid and accurate diagnosis of bloodstream infections in newborns and children with suspected sepsis. J Clin Microbiol 2011; 49:2252.
- Dhanani S, Cox PN. Infectious syndromes in the pediatric intensive care unit. In: Fuhrman & Zimmerman's Pediatric Critical Care, 4th edition, Fuhrman BP, Zimmerman JJ. (Eds), Elsevier Saunders, Philadelphia 2011. p.1336.
- van Waardenburg DA, Jansen TC, Vos GD, Buurman WA. Hyperglycemia in children with meningococcal sepsis and septic shock: the relation between plasma levels of insulin and inflammatory mediators. J Clin Endocrinol Metab 2006; 91:3916.
- Jansen TC, van Bommel J, Mulder PG, et al. The prognostic value of blood lactate levels relative to that of vital signs in the pre-hospital setting: a pilot study. Crit Care 2008; 12:R160.
- Levy B, Perez P, Gibot S, Gerard A. Increased muscle-to-serum lactate gradient predicts progression towards septic shock in septic patients. Intensive Care Med 2010; 36:1703.
- Scott HF, Donoghue AJ, Gaieski DF, et al. The utility of early lactate testing in undifferentiated pediatric systemic inflammatory response syndrome. Acad Emerg Med 2012; 19:1276.
- Marshall JC, Reinhart K, International Sepsis Forum. Biomarkers of sepsis. Crit Care Med 2009; 37:2290.
- Kaplan JM, Wong HR. Biomarker discovery and development in pediatric critical care medicine. Pediatr Crit Care Med 2011; 12:165.
- Luaces-Cubells C, Mintegi S, García-García JJ, et al. Procalcitonin to detect invasive bacterial infection in non-toxic-appearing infants with fever without apparent source in the emergency department. Pediatr Infect Dis J 2012; 31:645.
- Maniaci V, Dauber A, Weiss S, et al. Procalcitonin in young febrile infants for the detection of serious bacterial infections. Pediatrics 2008; 122:701.
- Hatzistilianou M, Rekliti A, Athanassiadou F, Catriu D. Procalcitonin as an early marker of bacterial infection in neutropenic febrile children with acute lymphoblastic leukemia. Inflamm Res 2010; 59:339.
- Juutilainen A, Hämäläinen S, Pulkki K, et al. Biomarkers for bacteremia and severe sepsis in hematological patients with neutropenic fever: multivariate logistic regression analysis and factor analysis. Leuk Lymphoma 2011; 52:2349.
- Herberg JA, Kaforou M, Wright VJ, et al. Diagnostic Test Accuracy of a 2-Transcript Host RNA Signature for Discriminating Bacterial vs Viral Infection in Febrile Children. JAMA 2016; 316:835.
- Zimmerman JJ, Sullivan E, Yager TD, et al. Diagnostic Accuracy of a Host Gene Expression Signature That Discriminates Clinical Severe Sepsis Syndrome and Infection-Negative Systemic Inflammation Among Critically Ill Children. Crit Care Med 2016.
- Marco D, Carlo S, Sara C, et al. Magicplex(TM) Sepsis Real-Time test to improve bloodstream infection diagnostics in children. Eur J Pediatr 2016; 175:1107.
- Kanegaye JT, Wilder MS, Molkara D, et al. Recognition of a Kawasaki disease shock syndrome. Pediatrics 2009; 123:e783.
- Salazar ML, Eiland LS. Intrathecal baclofen withdrawal resembling serotonin syndrome in an adolescent boy with cerebral palsy. Pediatr Emerg Care 2008; 24:691.
- Rigoli G, Terrini G, Cordioli Z. Intrathecal baclofen withdrawal syndrome caused by low residual volume in the pump reservoir: a report of 2 cases. Arch Phys Med Rehabil 2004; 85:2064.
- Alden TD, Lytle RA, Park TS, et al. Intrathecal baclofen withdrawal: a case report and review of the literature. Childs Nerv Syst 2002; 18:522.
- Zuckerbraun NS, Ferson SS, Albright AL, Vogeley E. Intrathecal baclofen withdrawal: emergent recognition and management. Pediatr Emerg Care 2004; 20:759.
- Kao LW, Amin Y, Kirk MA, Turner MS. Intrathecal baclofen withdrawal mimicking sepsis. J Emerg Med 2003; 24:423.
- Systemic inflammatory response syndrome
- - Age groups
- - Severity
- Risk factors
- Other pathogens
- Culture-negative sepsis
- CLINICAL MANIFESTATIONS
- Physical findings
- - Infection
- - Systemic inflammatory response syndrome
- - Shock
- - Other physical findings
- Laboratory studies
- DIFFERENTIAL DIAGNOSIS