Introduction
Background
Sepsis is a problem that presents a management challenge to those who care for infants and children; however, early recognition and intervention clearly improves the outcome for infants and children with infections or intoxications that lead to sepsis. Generally, sepsis is considered to comprise a spectrum of disorders that result from infection by bacteria, viruses, fungi, or parasites or the toxic products of these microorganisms. Bacteremia, viremia, fungemia, and parasitemia refer to bloodstream invasions that may be associated with fever but have no other signs or symptoms of circulatory compromise or end-organ malperfusion or dysfunction.
For further details of topics not fully discussed here, please refer to the particular articles (eg, Bacteremia, Herpes Simplex Virus Infection, Candidiasis, Malaria). Additionally, neonatal sepsis is discussed in a separate article (see Neonatal Sepsis).
The spectrum of sepsis ranges from microbial invasion of the bloodstream or intoxication with early signs of circulatory compromise, including tachycardia, tachypnea, peripheral vasodilation, and fever (or hypothermia), to full-blown circulatory collapse with multiorgan system failure and death. All these manifestations are part of the more appropriately termed systemic inflammatory response syndrome (SIRS), which is used interchangeably with sepsis to signify any of these manifestations, whatever the etiology. SIRS results from an insult, whether infectious, traumatic, chemical, malignant, autoimmune, or idiopathic, and the host response that follows. The outcome depends on the intricate interplay of upregulating and downregulating cytokines and inflammatory cells and the direct effects of the insult itself.
In recent years, experts have come together to develop a consensus on the definitions of sepsis, SIRS, severe sepsis and septic shock.1 Age-related variables have been applied to the definition of SIRS and sepsis. The definition of SIRS now requires either fever or WBC involvement to meet the criteria.
Pathophysiology
Fever is the most common presenting symptom of children with SIRS. Fever is one component of the triad of hyperthermia (or hypothermia), tachypnea, and tachycardia that typifies the earliest, mildest manifestation of SIRS. If SIRS is identified and reversed early, the subsequent inflammatory cascade can often be avoided or mitigated. However, in some situations, further damage occurs because the insult or the resultant host immune response is too great. This damage can result in increased cardiac output, peripheral vasodilation, increased tissue oxygen consumption, and a hypermetabolic state (ie, warm shock). If SIRS is not identified and reversed early, cardiac output may fall, peripheral vascular resistance may increase, and shunting of blood may ensue (ie, cold shock). This results in resultant tissue hypoxia, end-organ dysfunction, metabolic acidosis, end-organ injury and/or failure, and death.
Frequency
United States
Risk of sepsis decreases with age; neonates are at the highest risk, with bacterial sepsis occurring in 1-10 per 1000 live births. SIRS remains an infrequent but significant cause of death among infants and children in the United States.
International
Incidence of sepsis in the developing world is somewhat higher than in the United States. However, reports are fewer, and precise figures are unavailable.
Mortality/Morbidity
Almost half of neonatal deaths are caused by sepsis, although advances in diagnosis and treatment have caused this rate to considerably decrease, especially in preterm infants. Again, the mortality rate tends to decrease as age increases in the pediatric population.
Race
No particular racial predilection is noted for sepsis, except that invasive bacterial infections are more common in Eskimos, American Indians, and individuals with hemoglobin SS disease.
Sex
Except for urosepsis, which may be more common in females, no sex predilection for sepsis is known.
Age
The risk of sepsis is inversely related to age. Therefore, sepsis is most often found in neonates, and its likelihood decreases with age.
Clinical
History
Obtain a complete history as part of the evaluation of the infant or child with possible systemic inflammatory response syndrome (SIRS). A parental report of measured (not tactile) fever can generally be assumed to be reliable.
- Discuss the child's activity level.
- Perform an age-appropriate evaluation of mental status.
- Ask about urine output because it is the most sensitive historical marker of dehydration and potential renal hypoperfusion.
- Ask the caregiver whether any of the following have been noted: a racing heart, rapid or labored breathing, cool extremities, or color changes.
- Identify exposures to infectious illnesses and other sources of insult.
- Verify immunization and drug allergy statuses.
Physical
Perform a complete physical examination of the infant or child with suspected SIRS.
- Subtle changes in vital signs (eg, minimal tachycardia, widened pulse pressure, minimal tachypnea, minimally delayed capillary refill) may be the first signs of impending SIRS.
- Hypotension, mental status changes, and anuria are late signs of SIRS.
- Hypothermia is often a more ominous sign than fever.
- Elicit localizing signs of infection.
- A petechial or purpuric rash associated with fever is of particular concern.
- Frequent reassessment during interventions is required.
Causes
Myriad bacteria, viruses, fungi, and parasites can cause SIRS. Among the bacterial causes of sepsis, some age-related patterns are observed.
- Early-onset neonatal sepsis: Streptococcus agalactiae, Escherichia coli, Haemophilus influenzae, and Listeria monocytogenes are the most frequent organisms encountered.
- Late-onset neonatal sepsis: Coagulase-negative Staphylococcus, Staphylococcus aureus, E coli, Klebsiella species, Pseudomonas aeruginosa, Enterobacter species, Candida species, S agalactiae, Serratia species, Acinetobacter species, and various anaerobes are some of the most commonly involved organisms.
- Sepsis in infancy
- Streptococcus pneumoniae and Neisseria meningitidis predominate in the United States and the developed world because conjugate H influenzae type b (Hib) vaccination has essentially eliminated disease caused by that organism.
- Hib, S pneumoniae, N meningitidis, and Salmonella species are the most frequent causes of bacterial sepsis among most infants worldwide.
- In regions where malaria occurs, Plasmodium falciparum is a frequent cause of SIRS in infancy.
- Sepsis in childhood: The same pathogens cause SIRS in childhood, although the presence of encapsulated organisms generally becomes less frequent as a child's immune response to polysaccharide antigens improves with age.
- Special considerations: Underlying conditions predispose to infection with particular pathogens.
- Acquired immunodeficiency syndrome (AIDS) predisposes to SIRS from various usual and unusual pathogens, particularly pneumococcus.
- Children with hemoglobin SS disease have a 400-fold increased risk of sepsis due to pneumococcus and Salmonella, among other pathogens.
- Congenital heart disease is a risk factor for endocarditis and SIRS.
- Genitourinary anomalies often increase the risk of urosepsis.
- Infants and children with significant burns are at risk for SIRS, caused by skin flora and nosocomial gram-negative pathogens in particular.
- Splenic dysfunction or absence, as well as complement, immunoglobulin, and properdin deficiency, predispose to sepsis due to encapsulated organisms.
- Infants and children with hematologic and solid-organ malignancies (before or during treatment) are at increased risk for SIRS from a considerable variety of organisms.
- Neonates, infants, and children who are hospitalized (particularly in the intensive care unit [ICU]) are at increased risk of SIRS.
- Those with indwelling devices or prosthetic material and other breaches in barrier protective function are also at increased risk of SIRS.
More on Sepsis |
 Overview: Sepsis |
| Differential Diagnoses & Workup: Sepsis |
| Treatment & Medication: Sepsis |
| Follow-up: Sepsis |
| References |
| Next Page » |
References
Goldstein B, Giroir B, Randolph A. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. Jan 2005;6(1):2-8. [Medline].
Rodriguez-Nunez A, Lopez-Herce J, Gil-Anton J, et al. Rescue treatment with terlipressin in children with refractory septic shock: a clinical study. Crit Care. Feb 2006;10(1):R20. [Medline].
Barton P, Kalil AC, Nadel S, et al. Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis. Pediatrics. Jan 2004;113(1 Pt 1):7-17. [Medline]. [Full Text].
Weiss KD. Safety, pharmacokinetics, and pharmacodynamics of drotrecogin alfa (activated) in children with severe sepsis. Pediatrics. Jan 2004;113(1 Pt 1):134. [Medline]. [Full Text].
Annane D, Sebille V, Charpentier C, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862-71. [Medline].
Arnal LE, Stein F. Pediatric septic shock: why has mortality decreased?-the utility of goal-directed therapy. Semin Pediatr Infect Dis. Apr 2003;14(2):165-72. [Medline].
Balci C, Sungurtekin H, Gurses E, et al. Usefulness of procalcitonin for diagnosis of sepsis in the intensive care unit. Crit Care. 7(1):85-90. [Medline]. [Full Text].
Bernard GR, Vincent JL, Laterre PF, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699-709. [Medline]. [Full Text].
Emonts M, Sweep FC, Grebenchtchikov N, et al. Association between high levels of blood macrophage migration inhibitory factor, inappropriate adrenal response, and early death in patients with severe sepsis. Clin Infect Dis. May 15 2007;44(10):1321-8. [Medline].
Eschenbach DA. Prevention of neonatal group B streptococcal infection. N Engl J Med. Jul 25 2002;347(4):280-1. [Medline].
Festa M, Mumby S, Nadel S, et al. Antioxidant protection against iron in children with meningococcal sepsis. Crit Care Med. Jul 2002;30(7):1623-9. [Medline].
Fish DN. Optimal antimicrobial therapy for sepsis. Am J Health Syst Pharm. Feb 15 2002;59 Suppl 1:S13-9. [Medline].
Fortenberry JD, Paden ML. Extracorporeal Therapies in the Treatment of Sepsis: Experience and Promise. Semin Pediatr Infect Dis. Apr 2006;17(2):72-79. [Medline].
Galban C, Montejo JC, Mesejo A, et al. An immune-enhancing enteral diet reduces mortality rate and episodes of bacteremia in septic intensive care unit patients. Crit Care Med. Mar 2000;28(3):643-8. [Medline].
Hallwirth U, Pomberger G, Zaknun D, et al. Monocyte phagocytosis as a reliable parameter for predicting early-onset sepsis in very low birthweight infants. Early Hum Dev. Apr 2002;67(1-2):1-9. [Medline].
Han YY, Carcillo JA, Dragotta MA, et al. Early reversal of pediatric-neonatal septic shock by community physicians is associated with improved outcome. Pediatrics. Oct 2003;112(4):793-9. [Medline]. [Full Text].
Healy DP. New and emerging therapies for sepsis. Ann Pharmacother. Apr 2002;36(4):648-54. [Medline].
Hoehn S, Dominguez TE. Lemierre's syndrome: an unusual cause of sepsis and abdominal pain. Crit Care Med. Jul 2002;30(7):1644-7. [Medline].
Jacobi J. Pathophysiology of sepsis. Am J Health Syst Pharm. Feb 15 2002;59 Suppl 1:S3-8. [Medline].
Kaplan SL. Bacteremia and septic shock. In: Textbook of Pediatric Infectious Diseases. 2004:810-25.
Kirby A, Goldstein B. Improved outcomes associated with early resuscitation in septic shock: do we need to resuscitate the patient or the physician?. Pediatrics. Oct 2003;112(4):976-7. [Medline]. [Full Text].
Kuhl DA. Current strategies for managing the patient with sepsis. Am J Health Syst Pharm. Feb 15 2002;59 Suppl 1:S9-13. [Medline].
Kumar A, Roberts D, Wood KE. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34:1589-96. [Medline].
Lebel MH, Tapiero B. Bacteremia, sepsis, and septic shock. In: Pediatric Infectious Diseases: Principles and Practice. 2002:279-95.
Llewelyn MJ, Cohen J. Tracking the microbes in sepsis: advancements in treatment bring challenges for microbial epidemiology. Clin Infect Dis. May 15 2007;44(10):1343-8. [Medline].
Mahieu LM, De Dooy JJ, Cossey VR, et al. Internal and external validation of the NOSEP prediction score for nosocomial sepsis in neonates. Crit Care Med. Jul 2002;30(7):1459-66. [Medline].
Marik PE. Definition of sepsis: not quite time to dump SIRS?. Crit Care Med. Mar 2002;30(3):706-8. [Medline].
Oddie S, Embleton ND. Risk factors for early onset neonatal group B streptococcal sepsis: case-control study. BMJ. Aug 10 2002;325(7359):308. [Medline]. [Full Text].
Offit PA, Peter G. The meningococcal vaccine--public policy and individual choices. N Engl J Med. Dec 11 2003;349(24):2353-6. [Medline].
Pera A, Byun A, Gribar S, et al. Dexamethasone therapy and Candida sepsis in neonates less than 1250 grams. J Perinatol. Apr-May 2002;22(3):204-8. [Medline].
Rihn TL. Innovation in sepsis management. Introduction. Am J Health Syst Pharm. Feb 15 2002;59 Suppl 1:S2-3. [Medline].
Rivers E, Nguyen B, Havstad S, et al. Early goal-directed therapy in the treatment of severe sepsis and septic shock. N Engl J Med. 2001;345:1368-77. [Medline]. [Full Text].
Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal disease. N Engl J Med. 2001;344:1378-88. [Medline].
Russell JA. Management of sepsis. N Engl J Med. 2006;355:1699-713.
Santana C, Guindeo MC, Gonzalez G, et al. Cord blood levels of cytokines as predictors of early neonatal sepsis. Acta Paediatr. Oct 2001;90(10):1176-81. [Medline].
Sparling PF. A plethora of host factors that determine the outcome of meningococcal infection. Am J Med. 2002;112:72-4. [Medline].
Stoll BJ, Hansen N, Fanaroff AA, et al. Changes in pathogens causing early-onset sepsis in very-low-birth-weightinfants. N Engl J Med. Jul 25 2002;347(4):240-7. [Medline]. [Full Text].
Stoll BJ, Hansen N, Fanaroff AA, et al. Late-onset sepsis in very low birth weight neonates: the experience of theNICHD Neonatal Research Network. Pediatrics. Aug 2002;110(2 Pt 1):285-91. [Medline]. [Full Text].
Terblanche M, Almog Y, Rosenson RS, Smith TS, Hackam DG. Statins and sepsis: multiple modifications at multiple levels. Lancet Infect Dis. May 2007;7(5):358-68. [Medline].
Towers CV, Briggs GG. Antepartum use of antibiotics and early-onset neonatal sepsis: the next 4years. Am J Obstet Gynecol. Aug 2002;187(2):495-500. [Medline].
Van Amersfoort ES, Van Berkel TJ, Kuiper J. Receptors, mediators, and mechanisms involved in bacterial sepsis and septic shock. Clin Microbiol Rev. Jul 2003;16(3):379-414. [Medline]. [Full Text].
Warren HS, Gonzalez RG, Tian D. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 38-2003. A 12-year-old girl with fever and coma. N Engl J Med. Dec 11 2003;349(24):2341-9. [Medline].
Further Reading
Keywords
sepsis, systemic inflammatory response syndrome, SIRS, septic shock, septicemia, blood infection, bloodstream infection, neonatal sepsis, bacteremia, viremia, fungemia, parasitemia, Streptococcus agalactiae, S agalactiae, Escherichia coli, Haemophilus influenzae, Listeria monocytogenes, Coagulase-negative Staphylococcus, Staphylococcus aureus, E coli, Klebsiella species, Pseudomonas aeruginosa, Enterobacter species, Candida species, Serratia species, Acinetobacter species, Streptococcus pneumoniae, Neisseria meningitidis, H influenzae type b (Hib), S pneumoniae, N meningitidis, Salmonella species, Plasmodium falciparum, pneumococcus, meningococcemia, bacteremia, hyperthermia, hypothermia, tachypnea, tachycardia, hemoglobin SS disease, congenital heart disease, genitourinary anomalies, urosepsis
