Scott L. Weiss, MD, MSCE, FCCM
Sepsis is about ten times less common in pediatric patients than in adults but nonetheless remains an important and potentially devastating public health problem for infants, children, and adolescents worldwide. Indeed, many recent public awareness campaigns about sepsis and the implementation of state-mandated regulations have centered around pediatric patients. For example, the deaths of 12-year-old Rory Staunton and 5-year-old Gabriella Galbo spurred New York’s Rory’s Regulations and Illinois’ Gabby’s Law, respectively. However, efforts toward consensus definitions, guideline development, epidemiologic surveillance, quality assurance, and research funding for pediatric sepsis lag in time and attention behind adult sepsis. Here are five important things to know about pediatric sepsis.
1. Pediatric sepsis is a common and critical public health problem for kids too.
Population-based studies of the prevalence of pediatric sepsis estimate 72-89 cases per 100,000 pediatric population in the United States, with over 50,000-75,000 hospitalizations for pediatric sepsis and an associated cost near $5 billion annually.1,2 Globally, there are an estimated 22 cases of pediatric severe sepsis per 100,000 person-years and 2,202 cases of neonatal sepsis per 100,000 live births, translating into 1.2 million cases of pediatric and 3 million cases of neonatal sepsis per year.3 Over 4% of all hospitalized patients younger than 18 years and 8% of pediatric intensive care unit (PICU) patients in the United States have sepsis.4–7 Although estimates are challenged by a lack of standardized data collection and inconsistent reporting, these data confirm that sepsis is common in pediatric patients.
Overall mortality for pediatric sepsis is 4%-11%.2,4,5,8,9 As in adult sepsis, most pediatric deaths are due to multiple organ dysfunction syndrome, with early deaths more common among previously healthy children.10–12 Mortality may be as low as 1%-5% for those admitted through a pediatric emergency department2,13 and as high as 12%-30% for children with septic shock who require intensive care.6,7,14–16 However, with a median age around 3 years (or younger) compared to 60-65 years for adults,7,17 the years of life lost following death is three to four times higher for pediatric sepsis.
2. As with adult sepsis, defining pediatric sepsis is a challenge.
In 2005, the International Pediatric Consensus Conference published definitions and clinical criteria for pediatric sepsis, severe sepsis, and septic shock.18 The overall framework was based on prevailing views of adult sepsis at the time and modified using age-based physiology. As in adult sepsis, this consensus intended uniformity for use in research studies, but was also adopted into clinical practice. The lack of specificity of the systemic inflammatory response syndrome criteria and confusion about the term “severe sepsis” have become problematic.19 For example, in the Sepsis Prevalence, Outcomes, and Therapies (SPROUT) study, there was only moderate agreement between physician diagnosis and consensus criteria for pediatric severe sepsis and septic shock (Kappa interrater reliability, 0.57).20
The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) definition better integrates sepsis pathobiology with content-valid criteria for sepsis and septic shock in adults.21 The conception of sepsis as “life-threatening organ dysfunction caused by a dysregulated host response to infection”21 should also be applicable to children. However, application of a validated, graded organ dysfunction score—similar to the Sequential (Sepsis) Organ Failure Assessment (SOFA) score—to children with infections to define sepsis is only starting to be established. Data from Leclerc et al, Schlapbach et al, and Matics and Sanchez-Pinto have tested the predictive validity of the Pediatric Logistic Organ Dysfunction-2 score and novel pediatric SOFA (pSOFA) scores.16,22,23 All three studies concluded that graded scales for organ dysfunction improved predictive validity relative to the 2005 severe sepsis criteria. Moreover, increasing data support the utility of hyperlactatemia in pediatric sepsis.11,24
Despite these parallels, revised criteria for pediatric sepsis need to consider that children with sepsis are not just “little adults with sepsis.”25 Rather, age—young or old—fundamentally modifies the pathobiology through which infection results in organ dysfunction. Simply overlaying age adjustments to the adult criteria will oversimplify pediatric sepsis.26
3. The presentation of pediatric septic shock is different from that of adults.
Early recognition and diagnosis of sepsis is as important for children as it is for adults. Both the American College of Critical Care Medicine (ACCM) and the United Kingdom’s National Institute for Health and Care Excellence (NICE) recognize pediatric septic shock as a medical emergency requiring interventions within the first hour.27,28 However, children—especially young children— may present with subtle or distinct symptoms and clinical signs.27 For example, while tachycardia and tachypnea are common, reliance on these vital sign abnormalities is confounded by their lack of specificity and response to fear and anxiety. Moreover, because blood pressure may be preserved until a late, critical point of illness, other measures of altered perfusion, such as capillary refill, pulse strength, and extremity temperature, should be used to assess for cardiovascular dysfunction. Alterations in mental status may also be more difficult to detect since confusion, lethargy, disorientation, and agitation may be more subtle in a child, difficult to normalize to developmental age, or erroneously attributed to ordinary sleep. In infants and very young children, symptoms that would ordinarily help to localize an infection may be difficult or impossible to determine. Finally, presentation with low cardiac output and increased systemic vascular resistance (“cold shock”) is much more common than the classic presentation of vasodilated, distributive shock.29
4. Children with sepsis benefit from many of the same general therapeutic strategies as adults.
As in adults, outcomes are best with a bundled, multiprofessional, therapeutic approach focused on early recognition, intravenous access, collection of blood cultures, rapid broad-spectrum antimicrobial therapy, and restoration of blood volume and organ perfusion.9,13,30 Crystalloid fluids are first-line therapy for children with shock, although controversy remains as to the preferential use of 0.9% saline or balanced fluids and the volume and speed over which to bolus fluids.31–34 Time to antimicrobials also seems to be important, although data are limited in children.35 The ACCM guidelines now recommend epinephrine (through peripheral access if necessary) as first-line vasoactive therapy over dopamine,27 supported by two randomized clinical trials.36,37 However, initial use of norepinephrine as a vasopressor is recommended for the subset of children with “warm shock.”27 Hydrocortisone is reserved for absolute adrenal insufficiency or persistent shock despite titration of epinephrine or norepinephrine.27 For refractory shock, venoarterial extracorporeal membrane oxygenation is often successful, with reported survival rates up to 80% for newborns and 50%-75% for older children.27,38
5. Sepsis can affect children and their families well beyond the intensive care unit.
Unfortunately, the experience of sepsis does not end in the ICU for many children and their families. Post-intensive care syndrome (PICS) in children encompasses functional deficits in physical, cognitive, emotional, and social health with a long-term impact on development and the family.39 Persistent functional disability in pediatric sepsis survivors at hospital discharge and beyond is evident in up to one-quarter (or more) of patients, along with an increased risk for hospital readmission and long-term mortality.7,40–43 In preliminary results of the Life After Pediatric Sepsis Evaluation (LAPSE) study presented at the Society of Critical Care Medicine’s (SCCM) 2018 annual Congress, close to 20% of pediatric sepsis survivors had not returned to their pre-illness quality of life after 12 months. Efforts to attend to the lingering effects of sepsis and critical illness, such as through SCCM’s THRIVE initiative, are necessary for children and their families.
- Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS. Trends in the epidemiology of pediatric severe sepsis. Pediatr Crit Care Med. 2013 Sep;14(7):686-693.
- Prout AJ, Talisa VB, Carcillo JA, et al. Children with chronic disease bear the highest burden of pediatric sepsis. J Pediatr. 2018 Aug;199;194-199.e1.
- Fleischmann-Struzek C, Goldfarb DM, Schlattmann P, Schlapbach LJ, Reinhart K, Kissoon N. The global burden of paediatric and neonatal sepsis: a systematic review. Lancet Respir Med. 2018 Mar;6(3):223-230.
- Balamuth F, Weiss SL, Neuman MI, et al. Pediatric severe sepsis in U.S. children’s hospitals. Pediatr Crit Care Med. 2014 Nov;15(9):798-805.
- Odetola FO, Gebremariam A, Freed GL. Patient and hospital correlates of clinical outcomes and resource utilization in severe pediatric sepsis. Pediatrics. 2007 Mar;119(3):487-494.
- Ruth A, McCracken CE, Fortenberry JD, Hall M, Simon HK, Hebbar KB. Pediatric severe sepsis: current trends and outcomes from the Pediatric Health Information Systems database. Pediatr Crit Care Med. 2014 Nov;15(9):828-838.
- Weiss SL, Fitzgerald JC, Pappachan J, et al; Sepsis Prevalence, Outcomes, and Therapies (SPROUT) Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network. Global epidemiology of pediatric severe sepsis: the sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015 May 15;191(10):1147-1157.
- Ames SG, Davis BS, Angus DC, Carcillo JA, Kahn JM. Hospital variation in risk-adjusted pediatric sepsis mortality. Pediatr Crit Care Med. 2018 May;19(5):390-396.
- Evans IVR, Phillips GS, Alpern ER, et al. Association between the New York sepsis care mandate and in-hospital mortality for pediatric sepsis. JAMA. 2018 Jul 24;320(4):358-367.
- Cvetkovic M, Lutman D, Ramnarayan P, Pathan N, Inwald DP, Peters MJ. Timing of death in children referred for intensive care with severe sepsis: implications for interventional studies. Pediatr Crit Care Med. 2015 Jun;16(5):410-417.
- Schlapbach LJ, MacLaren G, Festa M, et al; Australian & New Zealand Intensive Care Society (ANZICS) Centre for Outcomes & Resource Evaluation (CORE) and Australian & New Zealand Intensive Care Society (ANZICS) Paediatric Study Group. Prediction of pediatric sepsis mortality within 1 h of intensive care admission. Intensive Care Med. 2017 Aug;43(8):1085-1096.
- Weiss SL, Balamuth F, Hensley J, et al. The epidemiology of hospital death following pediatric severe sepsis: when, why, and how children with sepsis die. Pediatr Crit Care Med. 2017 Sep;18(9):823-830.
- Paul R, Melendez E, Stack A, Capraro A, Monuteaux M, Neuman MI. Improving adherence to PALS septic shock guidelines. Pediatrics. 2014 May;133(5):e1358-e1366.
- De Souza DC, Shieh HH, Barreira ER, Ventura AM, Bousso A, Troster EJ; LAPSES Group. Epidemiology of sepsis in children admitted to PICUs in South America. Pediatr Crit Care Med. 2016 Aug;17(8):727-734.
- Schlapbach LJ, Straney L, Alexander J, et al; ANZICS Paediatric Study Group. Mortality related to invasive infections, sepsis, and septic shock in critically ill children in Australia and New Zealand, 2002-13: a multicentre retrospective cohort study. Lancet Infect Dis. 2015 Jan;15(1):46-54.
- Matics TJ, Sanchez-Pinto LN. Adaptation and validation of a Pediatric Sequential Organ Failure Assessment score and evaluation of the Sepsis-3 definitions in critically ill children. JAMA Pediatr. 2017 Oct 2;171(10):e172352.
- Rhodes A, Phillips G, Beale R, et al. The Surviving Sepsis Campaign bundles and outcome: results from the International Multicentre Prevalence Study on Sepsis (the IMPreSS study). Intensive Care Med. 2015 Sep;41(9):1620-1628.
- 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 Jan;6(1):2-8.
- Scott HF, Deakyne SJ, Woods JM, Bajaj L. The prevalence and diagnostic utility of systemic inflammatory response syndrome vital signs in a pediatric emergency department. Acad Emerg Med. 2015 Apr;22(4):381-389.
- Weiss SL, Fitzgerald JC, Maffei FA, et al; SPROUT Study Investigators and Pediatric Acute Lung Injury and Sepsis Investigators Network. Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study. Crit Care. 2015 Sep 16;19:325.
- Singer M, Deutschman CS, Seymour CW, et al. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016 Feb 23;315(8):801-810.
- Leclerc F, Duhamel A, Deken V, Grandbastien B, Leteurtre S; Groupe Francophone de Réanimation et Urgences Péediatriques (GFRUP). Can the pediatric logistic organ dysfunction-2 score on day 1 be used in clinical criteria for sepsis in children? Pediatr Crit Care Med. 2017 Aug;18(8):758-763.
- Schlapbach LJ, Straney L, Bellomo R, MacLaren G, Pilcher D. Prognostic accuracy of age-adapted SOFA, SIRS, PELOD-2, and qSOFA for in-hospital mortality among children with suspected infection admitted to the intensive care unit. Intensive Care Med. 2018 Feb;44(2):179-188.
- Scott HF, Brou L, Deakyne SJ, Kempe A, Fairclough DL, Bajaj L. Association between early lactate levels and 30-day mortality in clinically suspected sepsis in children. JAMA Pediatr. 2017 Mar 1;171(3):249-255.
- Weiss SL, Deutschman CS. Are septic children really just “septic little adults”? Intensive Care Med. 2018 Mar;44(3):392-394.
- Schlapbach LJ, Javouhey E, Jansen NJG. Paediatric sepsis: old wine in new bottles? Intensive Care Med. 2017 Nov;43(11):1686-1689.
- Davis AL, Carcillo JA, Aneja RK, et al. The American College of Critical Care Medicine clinical practice parameters for hemodynamic support of pediatric and neonatal septic shock: executive summary. Pediatr Crit Care Med. 2017 Sep;18(9):884-890.
- [No authors listed]. Sepsis: recognition, diagnosis and early management: © NICE (2017) Sepsis: recognition, diagnosis and early management. BJU Int. 2018 Apr;121(4):497-514.
- Ceneviva G, Paschall JA, Maffei F, Carcillo JA. Hemodynamic support in fluid-refractory pediatric septic shock. Pediatrics. 1998 Aug;102(2):e19.
- Balamuth F, Weiss SL, Fitzgerald JC, et al. Protocolized treatment is associated with decreased organ dysfunction in pediatric severe sepsis. Pediatr Crit Care Med. 2016 Sep;17(9):817-822.
- Emrath ET, Fortenberry JD, Travers C, McCracken CE, Hebbar KB. Resuscitation with balanced fluids is associated with improved survival in pediatric severe sepsis. Crit Care Med. 2017 Jul;45(7):1177-1183.
- Weiss SL, Keele L, Balamuth F, et al. Crystalloid fluid choice and clinical outcomes in pediatric sepsis: a matched retrospective cohort study. J Pediatr. 2017 Mar;182:304-310.e10.
- Ranjit S, Natraj R, Kandath SK, Kissoon N, Ramakrishnan B, Marik PE. Early norepinephrine decreases fluid and ventilatory requirements in pediatric vasodilatory septic shock. Indian J Crit Care Med. 2016 Oct;20(10):561-569.
- Sankar J, Ismail J, Sankar MJ, CPS, Meena RS. Fluid bolus over 15-20 versus 5-10 minutes each in the first hour of resuscitation in children with septic shock: a randomized controlled trial. Pediatr Crit Care Med. 2017 Oct;18(10):e435-e445.
- Weiss SL, Fitzgerald JC, Balamuth F, et al. Delayed antimicrobial therapy increases mortality and organ dysfunction duration in pediatric sepsis. Crit Care Med. 2014 Nov;42(11):2409-2417.
- Ramaswamy KN, Singhi S, Jayashree M, Bansal A, Nallasamy K. Double-blind randomized clinical trial comparing dopamine and epinephrine in pediatric fluid-refractory hypotensive septic shock. Pediatr Crit Care Med. 2016 Nov;17(11):e502-e512.
- Ventura AM, Shieh HH, Bousso A, et al. Double-blind prospective randomized controlled trial of dopamine versus epinephrine as first-line vasoactive drugs in pediatric septic shock. Crit Care Med. 2015 Nov;43(11):2292-2302.
- MacLaren G, Butt W, Best D, Donath S. Central extracorporeal membrane oxygenation for refractory pediatric septic shock. Pediatr Crit Care Med. 2011 Mar;12(2):133-136.
- Manning JC, Pinto NP, Rennick JE, Colville G, Curley MAQ. Conceptualizing post intensive care syndrome in children: the PICS-p framework. Pediatr Crit Care Med. 2018 Apr;19(4):298-300.
- Pinto NP, Rhinesmith EW, Kim TY, Ladner PH, Pollack MM. Long-term function after pediatric critical illness: results from the survivor outcomes study. Pediatr Crit Care Med. 2017 Mar;18(3):e122-e130.
- Farris RW, Weiss NS, Zimmerman JJ. Functional outcomes in pediatric severe sepsis: further analysis of the researching severe sepsis and organ dysfunction in children: a global perspective trial. Pediatr Crit Care Med. 2013 Nov;14(9):835-842.
- Czaja AS, Zimmerman JJ, Nathens AB. Readmission and late mortality after pediatric severe sepsis. Pediatrics. 2009 Mar;123(8):849-857.
- Als LC, Nadel S, Cooper M, Pierce CM, Sahakian BJ, Garralda ME. Neuropsychologic function three to six months following admission to the PICU with meningoencephalitis, sepsis, and other disorders: a prospective study of school-aged children. Crit Care Med. 2013 Apr;41(4):1094-1103.