Pediatric Sepsis Update

By Jennifer Robertson, MD
Attending Physician – Emergency Medicine
Cleveland Clinic

General Info

Worldwide, sepsis is the most common cause of death in children (1).  According to the World Health Organization (WHO), approximately 6 million children die every year from sepsis (2). While studies have shown that the incidence of sepsis is rising in the United States (US) (3), fatality from sepsis in US children is declining. Between 1995 and 2005, the case fatality rate decreased from 10.3% to 8.9% (3). This is likely due to our better understanding of the pathophysiology and the need for early, aggressive treatment.

Recap Basics

Sepsis is defined as infection plus a systemic inflammatory response (4). Infection can be documented or presumed and is any “pathologic process caused by the invasion of normally sterile tissue, fluid or body cavity by pathogenic microorganisms” (4).  A  systemic inflammatory response may be demonstrated by a variety of signs and symptoms (4), but the SIRS (Systemic Inflammatory Response Syndrome) criteria developed by Bone et al in 1992 (5) is commonly used in the adult population.

In children, the concepts of adult sepsis are the same in that sepsis includes both infection and an inflammatory response. However, due to developmental stages, physiologic differences, and age-appropriate vital signs, the criteria vary (1,6). In 2005, the International Pediatric Sepsis Consensus modified the adult SIRS and sepsis criteria to incorporate age suitable physiologic variables.  Additionally, the authors defined various organ dysfunction categories, severe sepsis, and septic shock specifically for children (6).

To have a positive pediatric SIRS screen, there must be at least two positive findings out of four major categories: core temperature, leukocyte count, respiratory rate, and heart rate. In addition, at least one of the following must be present, regardless of the other two criteria:  (a) core temperature > 38.5°C or < 36°C or (b) elevated or depressed leukocyte count for age or > 10% bands.  Other criteria include a mean respiratory rate > 2 standard deviations (SD) above normal for age, mean heart rate > 2 SD above normal for age or unexplained persistent tachycardia for at least 30 minutes, bradycardia in children < 1 year of age that is < 10th percentile for age or unexplained bradycardia for at least 30 minutes. It is important to note that other causes of the criteria must be ruled out including trauma, medication, and congenital disorders.  Goldstein et al provides an excellent reference for the review of age-appropriate vital signs and laboratory markers (6).

As previously mentioned, infection is also a necessary criterion for the diagnosis of sepsis. In children, this is defined as any documented or suspected infection caused by a pathogen associated with a high probability of infection (6). Evidence of infection includes findings on exam, radiographs, or laboratory tests. Severe sepsis in children must include sepsis plus cardiovascular dysfunction or acute respiratory distress syndrome or two or more other organ dysfunctions. Goldstein et al provides a comprehensive list of organ dysfunction criteria including cardiovascular, respiratory, neurologic, hematologic, renal and hepatic (6). The PELOD-2 (Pediatric Logistic Organ Dysfunction) Score, created by Leteurtre et al is also a useful reference for determining the severity of organ dysfunction in children (7,8).

Finally, septic shock in children is defined as sepsis plus cardiovascular organ dysfunction. Cardiovascular dysfunction may include a decrease in systolic blood pressure > 2 SD below normal for age, the need for vasopressors, decreased urine output, metabolic acidosis, and arterial lactate > 2 times the upper limit of normal (6). Comprehensive criteria are available in the table by Goldstein et al (6). It is important to note that in children, tachypnea may be a warning sign of inadequate perfusion. Additionally, tachycardia may occur much later than adults and is a true sign of hemodynamic compromise. This underscores the importance of early, goal-directed treatment (6,9).

What’s New

In 2012, the Surviving Sepsis Campaign updated management recommendations for severe sepsis and septic shock, both in adults and children (9). A committee of 68 experts representing 30 international organizations gathered to develop the guidelines.  The following is a non-comprehensive list of their recommendations. Please refer to Dellinger et al for a full report (9).

1. Initial resuscitation

  • For respiratory distress and hypoxemia, supply oxygen by face mask, high flow nasal cannula, or nasopharyngeal continuous positive airway pressure (CPAP). Mechanical ventilation may be needed. Sedation should be used.
  • When a central line is not available, it is acceptable to use an intravenous (IV) or intraosseous (IO) line for fluids and inotropes.
  • If possible, resuscitate with fluids and/or inotropes prior to mechanical ventilation to avoid hemodynamic collapse. Give isotonic crystalloids or albumin with boluses of up to 20mL/kg over 5-10 min, titrate to reverse hypotension and increase urine output. Give inotropes and not fluids if hepatomegaly or rales are present or is not responsive to fluids. Consider transfusion in those with hemolytic anemias.
  • Patients with low cardiac output and elevated systemic vascular resistance states should be given vasodilator therapies in addition to inotropes.
  • Do not rely on lactate as children commonly have normal lactates in septic shock. You may be able to trend lactates.
  • Evaluate for and treat pneumothorax, pericardial tamponade, or endocrine emergencies.
  • Initial endpoints include capillary refill of < 2 seconds, normal blood pressure for age, normal pulses, warm extremities, urine output >1 mL/kg/hr, and normal mental status. ScvO2 saturation greater than or equal to 70 % and cardiac index between 3.3 and 6.0 L min-1 m-2 should be targeted.

2. Antibiotics

  • Administer within one hour of identification of severe sepsis.
  • Obtain blood cultures prior to antibiotics but should not delay administration.
  • Empiric drug(s) of choice should be used per local recommendations.
  • Give clindamycin and anti-toxin therapies for toxic shock syndrome.
  • Give oral antibiotics for Clostridium difficile colitis if possible.

3. Extracorporeal membrane oxygenation (ECMO)

Consider for refractory pediatric septic shock and respiratory failure.

4. Corticosteroids

Give hydrocortisone to children with refractory shock and suspected adrenal insufficiency.

*Of note, the largest pediatric sepsis cohort to date (REsearching severe Sepsis and Organ dysfunction in children: a gLobal perspective, or RESOLVE), giving routine corticosteroids has shown no improvement in outcomes in pediatric sepsis (10).

5. Protein C and Activated Protein Concentrate

No recommendation, however the RESOLVE trial showed no benefit to activated protein C (11).

6. Blood and Plasma

  • During resuscitation and low superior vena cava oxygenation, target a hemoglobin of 10g/dL.
  • After stabilization, a hemoglobin of at least 7.0 g/dL should be maintained.
  • Give plasma in children with sepsis-induced thrombotic purpura disorder.

These very ill children obviously require urgent intensive care unit (ICU) admission. Although not relevant to emergency department resuscitation, it is interesting to ascertain the severity of illness upon admission, as this is prognostic of mortality (12). The Pediatric Risk of Mortality (PRISM) III score is a useful tool to determine severity of illness (12, 13, 14, 15). It is an improved version of the original PRISM score (13, 16) and is based on data collected from 32 pediatric intensive care units using 11,165 admissions. Calculators are online to help clinicians navigate the scoring system.

Bottom Line/Pearls & Pitfalls

Pearls regarding resuscitation in pediatric sepsis include:

  1. Early resuscitation
  2. Institution of specific antibiotic(s)
  3. Do not rely on the lactate to guide care
  4. There are many online tools/bundles that can assist with management and in determining severity of disease

Further Reading

    • Goldstein B, Giroir B, Randolph AR, et al. International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics. Pediatr Crit Care Med 2005; 6: 2-8.
    • Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. Intensive Care Med 2013; 39: 165-228.
    • Kissoon NK, Carcillo JA, Espinosa V, et al. World Federation of Pediatric Intensive Care and Critical Care Societies: Global Sepsis Initiative. Pediatr Crit Care Med 2011; 12: 494-503.


  1. Watson RS, Carcillo JA.  Scope and Epidemiology of Pediatric Sepsis. Pediatr Crit Care Med 2005; 6 (Suppl): S3-S5.
  2. The World Health Report 1996: Fighting Disease, Fostering Development. Geneva, World Health Organization, 1996.
  3. Hartman ME, Linde-Zwirble WT, Angus DC, et al. Trends in the Epidemiology of Pediatric Severe Sepsis. Pediatr Crit Care Med 2013; 14 (7): 686-93.
  4. Levy  MM, Fink MP, Marshall JC, et al. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference.  Crit Care Med 2003; 31 (4): 1250-56.
  5. Bone RC, Balk RA, Cerra FB, et al.  Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis. Chest 1992; 101: 1644-55.
  6. Goldstein B, Giroir B, Randolph AR, et al. International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics. Pediatr Crit Care Med 2005; 6: 2-8.
  7. Leteurtre S, Martinot A, Duhamel A, et al. Development of a Pediatric Multiple Organ Dysfunction Score: Use of Two Strategies. Med Decis Making 1999; 19 (4): 399-410.
  8. Leteurtre S, Duhamel A, Salleron J, et al. PELOD-2: An Update of the Pediatric Logistic Organ Dysfunction Score. Crit Care Med 2013; 41 (7): 1761-73.
  9. Dellinger RP, Levy MM, Rhodes A, et al. Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012. Intensive Care Med 2013; 39: 165-228.
  10. Zimmerman JJ, Williams MD. Adjunctive Corticosteroid Therapy in Pediatric Severe Sepsis: Observations from the RESOLVE study. Pediatr Crit Care Med 2011; 12: 2-8.
  11. Nadal  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 (9564): 836-843.
  12. Costa G, Delgado AF, Ferraro A, et al. Application of the Pediatric Risk of Mortality Score (PRISM) and Determination of Mortality Risk Factors in a Tertiary Pediatric Intensive Care Unit. Clinics 2010; 65 (11): 1087-92.
  13. Pollack MM, Patel KM, Ruttiman UE. PRISM III: An Updated Pediatric Risk of Mortality Score. Crit Care Med 1996; 24 (5): 743-52.
  14. Karambelkar GR, Mane SV, Agarkhedkar, et al. The Relevance of 24 Hour PRISM III Score in Predicting Mortality in Pediatric Intensive Care Unit. Int J Pharm Biomed Sci 2012; 3(4): 214-219.
  15. Taori RN, Lahiri KR, Tullu MS. Performance of PRISM (Pediatric Risk of Mortality) Score and PIM (Pediatric Index of Mortality) Score in a Tertiary Care Pediatric ICU. Indian J Pediatr 2010; 77 (3): 267-271.
  16. Pollack MM, Ruttimann UE, Getson PR. Pediatric Risk of Mortality (PRISM) Score. Crit Care Med 1988; 16(11): 1110-6.
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