Pediatric Sepsis
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Transcript of Pediatric Sepsis
JOURNAL READING
PEDIATRIC SEPSISPRESENTED BY : DENA KARINA F
Tropical Infection Division
Department of Child Health FMUI - RSCM
INTRODUCTION
INTRODUCTION
Sepsis is the leading cause of death in children worldwide. Childhood pneumonia is the most common cause of
pediatric sepsis; it is also the leading cause of mortality in children less than 5 y of age
The management of pediatric sepsis must be tailored to the child’s age and immune capacity, and to the site, severity, and source of the infection.
many survivors of severe infection have chronic health impairments.
Developed country3%
Developing country97%
Childhood PneumoniaN = 156 million cases/year
worldwide
Rudan I, et al. Epidemiology and etiology of childhood pneumonia. Bull World Health Organ 2008; 86:408-16
Contaminated water
Poor sanitation
Indoor air pollution
CrowdingLow birth weight
Insufficient nutrition
Insufficient
immunization
pathogens invade and
multiply relatively
unchecked in body
Developing Country
INTRODUCTION
HIGHLIGHTS
Pediatric-specific issues related to the definition of sepsis and its epidemiology and management
The capacity of the immune system to respond to infection develops over early life
Primary immune deficiencies that should be considered in children recurrently infected with specific types of organisms.
Infection-related syndromes that primarily affect children
PEDIATRIC DEFINITIONS OF SEPSIS, SEVERE SEPSIS, AND SEPTIC SHOCK
DEFINITION
Sepsis• presence (probable or documented) of infection
together with systemic manifestations of infection
Severe sepsis
• (+) end organ system involvement
Septic shock
• (+) cardiovascular dysfunction that is not resolved by initial fluid resuscitation
DEFINITION - DIFFERENCES
One major difference in the definition of sepsis in children vs. adults are the age-specific cutoffs for physiologic and organ system-related laboratory parameters
The healthy pediatric cardiovascular system can maintain cardiac output by employing extreme tachycardia for a prolonged period without inducing myocardial ischemia.
Compared with adults, hypotension presents later in children and often portends imminent and potentially non-reversible cardiovascular collapse
Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus confer -ence: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6:2-8;
Goldstein B, Giroir B, Randolph A; International Consensus Conference on Pediatric Sepsis. International pediatric sepsis consensus confer -ence: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med 2005; 6:2-8;
From Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012
RESPONSE TO INFECTION BY THE DEVELOPING IMMUNE SYSTEM
sterile, intrauterine environment
eco -logically complex and
changing microbiologic
milieu
• Neonates are most profoundly immune compromised (innate and adaptive immunity)
• primary mitigating factor during the first 6 mo of life is transplacentally acquired maternal IgG and IgA
• markedly increased susceptibility to severe infection from various organisms, particularly viruses (esp < 2 years old) and encapsulated bacteria.
full immune competence is reached in teenage years
DEVELOPING IMMUNE SYSTEMA child’s immune system is remarkably different from adults in terms of innate and adaptive immune function
INNATE IMMUNITY : NEONATES
• less responsive to pathogen-associated molecular patterns (PAMPs)
• diminished adhesion and extravasation activity
• produce fewer pro-inflammatory cytokines
• diminished antigen presentation activity to adaptive immune cells
Phagocytes
• NK cells are less cytotoxic• complement levels are only 10–
70% of adult level
NK Cells & Complements
ADAPTIVE IMMUNITY : NEONATEST-
Cell • Levels >>
than adult• Poor
function, in part due to low production of interleukin-2 (IL-2)
CD
4 +
T h
elp
er
cells
• skewed toward Th-2 (humoral) responses in the neonate due to low production of interferon-γ (IFN γ )
CD
8 +
T h
elp
er
cells • cytotoxi
c CD8+ T cells are less active
B-C
ell • abundant in
the neonate, but pre dominantly naïve, produce mostly IgM
• poorly responsive to capsular polysaccharides
EPIDEMIOLOGY AND CLINICAL MANIFESTATIONS OF PEDIATRIC SEPSIS
EPIDEMIOLOGY OF PEDIATRIC SEPSIS
1995 2000 20050
0.2
0.4
0.6
0.8
1
0.560.63
0.89
Prevalensi Kasus severe sepsis di Amerika Serikat
(per 1000 anak)
common pathogens causing sepsis in children differ not only by local geography but by age and medical co-morbidities.
despite advances in microbiologic detection methods, the underlying cause of sepsis remains unknown in up to 75% of pediatric cases
COMMON ETIOLOGY OF BACTERIAL SEPSISAge Pathogen Comments
Neonates - group B streptococci (GBS)
- enteric gram-negative rods, especially Escherichia coli
Most common bacterial pathogen causing late-onset sepsis
Infants Bordatella pertussis
Neisseria meningitidis
cause a severe illness in young infantcharacterized by recurrent episodes of gagging, apnea, cyanosis, and bradycardia and with high mortality in those that develop respiratory failure and pulmonary hypertensionisolated from infants with severe sepsis
Children H. influenzae type b one of the most common causes of bacterial sepsis in children <5 y old
S. pneumoniae The leading cause of hospitalization for pneumonia in childhood
Neisseria meningitidis isolated from young children with severe sepsiscausing meningococcemia, may cause purpura fulminans (in 25% children with meningococcemia)
Age Pathogen Comments
Children S. aureus and Streptococcus pyogenes (group A strep or GAS)
May cause severe necrotizing pneumonias accompanied by septic shock in otherwise healthy children
PseudomonasAcinetobacter, Burkholderia spp.
• most commonly identified in children hospitalized for prolonged periods with persistent indwelling devices such as intravascular catheters or tracheostomies
• in oncology and other immune-suppressed patients who have had multiple courses of broad-spectrum antibiotics
coagulase-negative staphylococci (CONS) and methicillin-resistant S. aureus (MRSA)
Nosocomial pathogen
Burkholderia pseudomallei, or meliodosis
seen in southeast Asia, can present with pulmonary symptoms and fever
The viral infection is thought to pre -cede and predispose children to bacterial invasion
Viral–bacterial co-infection occurs in up to 23% of cases of severe pneumonia, resulting in a higher likelihood of respiratory failure and septic shock
Aside from influenza virus, older children and adolescents with healthy immune and cardiorespiratory systems are rarely hospitalized for viral sepsis
COMMON ETIOLOGY OF VIRAL SEPSIS
COMMON ETIOLOGY OF VIRAL SEPSISAge Pathogen Comments
Neonates - herpes simplex virus (HSV),
- enterovirus, and- parechoviruses
May cause overwhelming viral sepsis in neonates
Infants Respiratory syncytial virus (RSV)
identified in the majority of infants hospitalized for bronchiolitis
Human metapneumovirus and rhinovirus
increasingly identified as a cause of hospitalization for bronchiolitis in infants
Children influenza one of the most common cause of viral sepsis in children
parainfluenza • most commonly stays in the upper airway causing croup mostly in healthy children
• can cause severe pneumonia in the very young and in children with compromised immune or respiratory symptoms
HSV, acute cytomegalovirus, adenovirus, or Epstein–Barr virus
May cause sepsis in profoundly immune-compromised children from cancer or HIV
COMMON ETIOLOGY OF VIRAL SEPSIS
Age Pathogen Comments
Children Rotavirus can lead to a profound diarrhea and sepsis-like picture in very young children
Dengue virus causes a sepsis syndrome typified by capillary leak and disseminated intravascular coagulation (DIC)
LESS COMMON ETIOLOGY OF SEPSIS
Pathogen Comments
Fungal pathogens, particularly Candida species
cause up to 10% of severe septic shock in children
tick-borne diseases, including Rocky Mountain Spotted Fever and ehrlichiosis
can present as encephalitis meeting criteria for sepsis
Salmonella species Can cause sepsis particularly in children with functional asplenia and those who are malnourished
Malaria—particularly Plasmodium falciparum
• cause sepsis in young children and HIV-infected children• sepsis is often seen in association with cerebral malaria
presenting with symptoms of altered mental status, convulsions, and acidosis
PRIMARY AND ACQUIRED IMMUNE DEFICIENCY IN SEPSIS
PRIMARY AND ACQUIRED IMMUNE DEFICIENCY IN SEPSIS it is critical to recognize recurring patterns of infection or
severe clinical presentations suggesting that the child may have an underlying immune deficiency
A thorough evaluation for a primary immune deficiency should include detailed medical history that includes :
gestation, birth, growth, development, and immunizations
a family history
history of prior infections with special attention to pathogens identified and sites of infection.
Principles and Practice of Pediatric Infectious Diseases. 4th ed. Eds: Long SS, Pickering LK, Prober CG. Edinburgh: Elsevier, 2012; pp 600-41
Principles and Practice of Pediatric Infectious Diseases. 4th ed. Eds: Long SS, Pickering LK, Prober CG. Edinburgh: Elsevier, 2012; pp 600-41
Acquired immune
deficiency
HIV infection
invasive fungal infections
opportunistic infection such
as disseminated mycobacterial
infection
infection with typical
Pathogens (eg. S. pneumonia)
significantly associated with disseminated infection from M. Tb
MANAGEMENT OF SEPSIS IN INFANTS AND CHILDREN COMPARED WITH ADULTS
PRINCIPLES
Of primary importance, as in adult patients with sepsis, is to provide empiric antimicrobial therapy that treats potential causative pathogens based on a patient’s age and exposure history.
One major difference in how children with refractory septic shock and/or refractory hypoxemia from severe respiratory tract infection are clinically managed compared with adults is a higher use of extracorporeal life support (ECLS) as rescue therapy.
aggressive fluid resuscitation strategy has been extrapolated to pediatric treatment recommendations for pediatric sepsis
CULTURES
Cultures as clinically appropriate before antimicrobial therapy if no significant delay ( [45 min) in the start of antimicrobial(s) (grade 1C).
At least 2 sets of blood cultures (both aerobic and anaerobic bottles) be obtained before antimicrobial therapy with at least 1 drawn percutaneously and 1 drawn through each vascular access device, unless the device was recently ( < 48 h) inserted (grade 1C)
From Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012
PRINCIPLES OF ANTIMICROBIAL THERAPY
From Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock, 2012
Brierly J, Carcillo JA, Choong K et al (2009) Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock:
2007 update from the American College of Critical Care Medicine. Crit Care Med 37:666–688
Algorithm stepwise management of hemodynamic support in infants and children.
Brierly J, Carcillo JA, Choong K et al (2009) Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock:
2007 update from the American College of Critical Care Medicine. Crit Care Med 37:666–688
Algorithm stepwise management of hemodynamic support in neonates
Brierly J, Carcillo JA, Choong K et al (2009) Clinical practice parameters for hemodynamic support of pediatric and neonatal patients in septic shock: 2007 update from the American College of Critical Care Medicine. Crit Care Med 37:666–688
FACTORS INFLUENCING PEDIATRIC SEPSIS-RELATED MORTALITY
FACTORS INFLUENCING PEDIATRIC SEPSIS-RELATED MORTALITYFactors Comments
Age • Children <12 mo old have the highest risk of death from sepsis (esp. infants born very prematurely).
• Compared with older children, infants have the highest incidence of severe sepsis but much of it is viral and most will survive hospitalization.
Gender • Mortality was less prominently associated with gender in children, although males are more likely to be hospitalized in infancy for severe infections
Associated medical condition
• majority of older children hospitalized with sepsis have underlying conditions impairing their immune or cardiorespiratory systems (e.g. malignancies and other chronic respiratory and cardiac conditions)
Site of Infection • endocarditis and CNS infections associated with the highest mortality rates (21.1% endocarditis, 17.1% CNS infections)
Pathogens • fungi, and infections with antibiotic-resistant bacteria, including MRSA, gram-negative bacilli, and nosocomial pathogens are associated with worse prognosis
Extent of systemic involvement
• Children who develop multiple organ system failure from sepsis have the lowest likelihood of surviving
THANK YOU
pathogen-associated molecular patterns (PAMPs)
Necrotizing pneumonia
Functional asplenia