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;

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

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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

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)


PRINCIPLES OF ANTIMICROBIAL THERAPY


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

Pediatric Sepsis

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