Sepsis

Introduction:

Sepsis is a clinical syndrome resulting from severe infection and activation of the systemic inflammatory response. It is characterized by immune dysregulation leading to a generalized pro-inflammatory cascade, microcirculatory derangements, and end-organ dysfunction. It is typically this dysregulated immune response, and not the infectious organism itself, that is responsible for multiple organ failure and adverse outcomes in sepsis.

Early recognition of sepsis is crucial to ensuring the best outcomes in children, as it is the leading cause of morbidity and mortality in children worldwide.

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Image from kidshealth.org

Definitions:

The following are definitions for sepsis in children, from the International Consensus Conference on Pediatric Sepsis:

Infection:

  • Suspected or proven infection with any pathogen.

Systemic inflammatory response syndrome:

  • Generalized inflammatory response defined by having 2 or more of the following (abnormal temperature or white cell count must be one of the criteria):
    • Abnormal core temp. (<36° C or >38.5° C)
    • Abnormal heart rate (>2 standard deviations above normal for age, or <10th centile for age if child is <1 year)
    • Elevated respiratory rate (>2 standard deviations above normal for age, or mechanical ventilation for acute lung disease).
    • Abnormal white cell count in circulating blood (above or below normal range for age, or >10% immature white cells)

Sepsis:

  • Systemic inflammatory response syndrome in presence of infection.

Septic shock:

  • Sepsis with cardiovascular dysfunction despite at least 40mL/kg of fluid resuscitation in one hour.

Refractory septic shock:

  • Fluid refractory: Persisting after ≥60mL/kg of fluid resuscitation.
  • Catecholamine resistant: Persisting despite treatment with catecholamines (dopamine and/or epinephrine, or norepinephrine infusion).

Epidemiology:

The overall global burden of sepsis is high, however the global incidence varies by region. Approximately 6-8% of patients were treated in a pediatric intensive care unit (PICU) for sepsis in North America, Europe, Australia and New Zealand, with an overall mortality of 21-32%. An estimated 15% of patients were treated for sepsis in PICUs in Asia and South America, with mortality rates of 40% and 11%, respectively. Similarly, about 25% were treated in PICUs in Africa with a mortality of 40%.

In the U.S., it has been approximated that there are over 42,000 cases of pediatric severe sepsis per year nationally (0.56 cases per 1,000 population per year).

Respiratory and blood infections are found in about two-thirds of sepsis cases worldwide, many of which are due to infections that are preventable by vaccines.

Risk Factors:

  • Age less than one month: Infants are at highest risk, especially those with a low birth weight
  • Chronic debilitating medical condition
  • Host immunosuppression
  • Serious injury
  • Large surgical incisions
  • Invasive devices (Foley catheters, chest tubes, etc.)
  • Recurrent UTIs due to urinary tract abnormalities

Pathogens:

Sepsis can be caused by bacterial, viral, fungal, parasitic, or rickettsial infections, with bacteria and viruses being the most common. The typical or important pathogens in sepsis are:

Early onset neonatal sepsis (occurring in the first 72 hrs of life):

  • Group B Streptococcus (GBS), and Gram negative bacilli (especially E. coli)
  • S. aureus and coagulase negative staphylococci, H. influenza, and enterococci
  • Listeria monocytogenes,

Late onset neonatal sepsis (72 hrs of life to one month of life):

  • Coagulase negative staphylococci
  • May also be caused by the same organisms as in early onset sepsis

Infants and young children:

  • S. pneumonia
  • N. meningitides
  • S. aureus and GAS
  • H. influenza type b
  • Bordetella pertussis

Infants and children in hospital:

  • Coagulase negative staphyloccci
  • MRSA
  • Gram negative organisms such as P. aeruginosa, Klebsiella species, E. coli, and Acinetobacter species

Other organisms

  • Fungal (e.g. Candida, or Aspergillus species)
  • Viral (influenza, RSV, human metapneumovirus, varicella, HSV)

Clinical Presentation:

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Image from blogs.cdc.gov

In general, sepsis should be suspected in any acute illness or in neonates if there is any change in the patient’s normal pattern of behavior. The diagnosis oftentimes is made using clinical judgment, since diagnostic criteria are primarily considered research criteria. Thus, a clinician should consider sepsis or septic shock if a child has a suspected or proven infection and has at least 2 of the following:

  • Core temperature <36° C or >38.5° C (<97° F or >101° F).
  • Inappropriate tachycardia (according to local criteria or advanced pediatric life support guidance).
  • Altered mental state (such as sleepiness, irritability, lethargy, floppiness).
  • Reduced peripheral perfusion or prolonged capillary refill.

Diagnostic Tests:

First tests to order include:

  • Complete blood count with differential
  • Serum glucose
  • Blood culture
  • Urine analysis and urine culture
  • Blood gases
  • Serum lactate, electrolytes, and creatinine
  • Liver function tests
  • Coagulation studies
  • C-reactive protein
  • Chest x-ray

Management:

Sepsis management requires quick recognition and special attention must be paid to educate and train all healthcare staff to enable appropriate triage and rapid treatment. Particular emphasis on early administration of antibiotics and fluid resuscitation is vital.

 

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Image adapted from www.wfpiccs.org

Consensus guidelines are available online through the Pediatric Sepsis Initiative. The Pediatric Advanced Life Support (PALS) Pocket Reference Card provides a summary algorithm. A general sequence for recognition and treatment is:

  1. Recognize signs of poor perfusion.
  2. Assess ABCs.
  3. Establish IV access and place patient on monitor.
  4. Fluid and electrolyte resuscitation.
  5. Infection control.
  6. Supplemental therapies.

 

Therapeutic endpoints include:

  • Normalized heart rate
  • Capillary refill <2 sec
  • Normal pulse quality
  • Warm extremities
  • Normalized blood pressure
  • Normal mental status
  • Urine output >1 mL/kg/hr.
  • No difference in peripheral and central pulses
  • Decreasing lactate
  • SvO2>70%
  • CVP>8 mmHg

Prognosis:

Severe sepsis, without treatment, has a mortality of more than 80%. With treatment, it is decreased to about 10% in children up to 19 years of age, with no difference in gender. Those with a pre-existing condition have a mortality of around 13% compared to 7% in previously healthy children.

Early recognition of sepsis and resuscitation, according to ACCM-PALS guidelines, resulted in a mean length of stay of 5.5 days in the intensive care unit and a mean length of stay of 8 days in the hospital.

References:

  1. American Heart Association. EC90-1053. Distributed by Channing Bete Co. Pediatric Advanced Life Support Pocket Reference Card. Available at http://shop.aha.channing-bete.com/onlinestore/storeitem.html?iid=180286. Accessed: Nov 9, 2011
  2. Butt W. Septic shock. Pediatr Clin North Am 2001; 48:601.
  3. 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.
  4. Hartman ME, Linde-Zwirble WT, Angus DC, Watson RS. Trends in the epidemiology of pediatric severe sepsis*. Pediatr Crit Care Med 2013; 14:686.
  5. Paul R, Neuman MI, Monuteaux MC, et al. Adherence to PALS Sepsis Guidelines and Hospital Length of Stay. Pediatrics 2012; 130:e273-80
  6. Plunkett A, Tong J. Sepsis in children. BMJ 2015. Jun 9; 350:h3017
  7. Pomerantz WJ, Weiss, S, et al. Systemic inflammatory response syndrome (SIRS) and sepsis in children: Definitions, epidemiology, clinical manifestations, and diagnosis. UpToDate. Available at http://www.uptodate.com/contents/systemic-inflammatory-response-syndrome...?
  8. 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.
  9. Silverman, AM. Septic shock: recognizing and managing this life-threatening condition in pediatric patients. Pediatr Emerg Med Pract. 2015 Apr;12(4):1-25
  10. Watson RS, Carcillo JA, Linde-Zwirble WT, Clermont G, Lidicker J, Angus DC. The epidemiology of severe sepsis in children in the United States. Am J Respir Crit Care Med. 2003; 167(5): 695-701.
  11. 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
  12. World Federation of Pediatric Intensive and Critical Care Societies. Pediatric Sepsis Initiative educational materials. Available at http://www.wfpiccs.org/education/doctors-nurses/documents/. Accessed: June 23, 2013.