Sepsis in children

1. Sepsis In Children
Presented by – Dr Anand Singh (DCH DNB )

2. Brief overview
 Sepsis is a clinical syndrome that complicates severe infection
and is characterized by –
- Systemic inflammatory response syndrome ( SIRS )
- Immune dysregulation
- Microcirculatory derangements
- End organ dysfunction

3. definitions
Cold shock – CFT >2 sec, decresed pulse, mottling of skin +
Warm shock – Flushed CFT, bounding pulse & absent mottling

5. MODS
(multi organ dysfunction )
Presence of altered organ
function such that homeostasis
cannot be maintained without
medical intervention

6. Septic shock is often discussed synonyms with distributive shock but septic process
usually involves more complex interaction of distributive, hypovolemic and
cardiogenic shock

7. Epidemology
Sepsis is single largest cause of child mortality accounting for more than
half of 7.6million pediatric deaths world wide
No incidence data is available from india
USA – incidence of severe sepsis 0.56 cases / 1000 population per year
Highest incidence are in infants 5.16/ 10000 – 70 % neonate & 4/5 of neonates
are LBW
Incidence fall dramitaclly in older children 0.2/1000 in 10 to 14 yrs old
“Big four” killers of children: pneumonia ( 37 % ), diarrhea, malaria, measles
Age and sex : Infants at a higher risk , Males > Females

8. Mortality:
In industrialized countries is estimated at 2 to 10%
(Dellinger R, Levy M, Rhodes A, et al. Surviving Sepsis Campaign:
international guidelines for management of severe sepsis and septic
shock.
Inten Care Med 2013;39:165–228 )
In developing countries has been documented to be as high as 50%
( India, Nigeria, Democratic Republic of the Congo, Pakistan, and
China account for approximately half of all deaths in children younger
than 5 yrs of age )
(Oliveira C, Nogueira de Sá FR, D Oliveira, et al. Time- and fluid-
sensitive resuscitation for hemodynamic support of children in septic
shockGuidelines in a pediatric intensive care unit in a developing world.
Pediatr Emerg Care 2008;24:810–5 )

10. Pathophysiology
Pro inflammatory cytokines, IL 1
Tissue factor expression on
endothelial cells by direct effect
Thrombin
Clots in micro vasculature
( seen in meningococci )
Also inhibit natural anti coagulant
APC & Antithrombin, thus prevents coagulation cascade
Production of PAI 1 which is
inhibitor of fibrinolysis
1. Capillary lekage due to endothelial damage
2. Adhesion molecule production on
endothelial cells & neutrophil & more
avctivates more neutrophil
3. Release of NO which lead to shock
CD 4 lymphocytes TH 1 phenotype relese inflamtory
cytokines TNF & IL 2
Over time TH 2 phenotype & release anti inflammatory
cytokines IL 4, 10 , 13
( due to stress hormones )
- Dampen immune response & deactivates Monocytes
- TNF causes apoptosis of lymphocytes so further
immunosupression
Viscious cycle of inlamation & coagulation leads to
Cardiovascular insufficiency & MODY & Death

11. ETIOLOGY
 Depends on age, community / hospital acquired, local epidemiology, season, site,
presence of immunofefeciency
 Neonates & young infants ( up to 3 months )
 Mainly gram –ve like klebsiella, E coli, Pseudomonas, Enterbacter & Citrobacter
 Staph aureus, enterococci & candida, listeria is less common
 POST NEONATAL PERIOD –
 More than 3 months - Streptococci pneumoniae, H influenza, meningococci
 Salmonella typhi & paratyphi are imp but less associated with severe sepsis
 Dengue & malaria for all ages ( sp in monsoon )
 Ricketsiae, leptospira, scrub typhus, spotted fever in epidemic settings
 TSS due to staph & streptococci

12. site specific infection
 ABM – S pnemoniae, H influenza, Meningococci
 Pneumonia & LRTI – influenza & para influenza, RSV, S
pneumonaie, H influenza, Mycoplasma
 UTI – E coli, klebsiella, proteus, ESBL
 GIT & Inta abdominal infection - E coli, anaerobes &
enterococci
 Skin & soft tissue infection – S aureus, Strep pyogens
 Necrotizing Fascitis – S aureus, S pyogens anaerobes
 Bone & joint infection – S aureus, Pneumococci, HiB

13. nosocomial infection
 Blood strem infection
 Health care associated pneumonia
 UTI
 Surgical site infection
 CD enterocolitis
Most common etiological agents like E coli,Klebsiella,
pseudomonas, Candida specially non albicans
( tropicalis )

14. In immunocompromised
children with cancer , transplant, immunosuppressive drugs, on
steroids, anatomical or functional asplenia, burn patients,
immunodeficiency
Humoral deficiency – capsulated organism like pneumococci,
meningococci , HiB
Cellular Defeciency – intracellular pathogen like mycobacterium,
salmonella, pneumocystis carinni
Phagocytic Defect – gram –ve bacteria, S aureus, Aspergillus

15.  Fungal infections especially candida species have been reported in 10
percent of pediatric patients with severe sepsis and septic shock. It is usually
seen in --
 ● Malignancy or other immunocompromising medical conditions
 ● Indwelling vascular catheters
 ● Prolonged neutropenia (>4 to 7 days)
 ● Recent broad spectrum antibiotic use

16. Factors associated with an increased risk for septic shock
 < 1 year of age
 Very low birth weight infants
 Prematurity
 Serious injury (eg major trauma, burns, or penetrating wounds)
 Chronic debilitating medical condition (eg static encephalopathy with
quadriplegia and frequent aspiration pneumonia, uncorrected congenital
heart disease, short gut syndrome)
 Host immunosuppression (malignancy, human immunodeficiency virus
infection, severe malnutrition, congenital immunodeficiency, sickle cell
disease and other disease with splenic dysfunction or immunomodulating
medications
 Large surgical incisions
 In dwelling vascular catheters or other invasive devices (eg endotracheal
tube, Foley catheter, chest tube)
 Urinary tract abnormalities with frequent infection

17. Clinical Feature

18. Clinical presentation
- No single diagnostic test or clinical sensitive rule but best approach is a high level of clinical
suspicion combined with the clinical history, vital signs, and physical examination.
- The PAT uses visual and auditory clues to quickly assess a child’s general appearance, work of
breathing, and circulation.
- Classical Initial signs include- change in tempratute (hyperthermia or hypothermia),tachypnea
tachycardia and change in mental status.-

19.  Clinical manifestations typically progress along a continuum of severity
from sepsis to severe sepsis (sepsis plus cardiac, respiratory, or dysfunction in two or
more other organ systems , septic
shock (persistent hemodynamic instability despite initial fluid therapy) and
multiple organ failure.

20. DIFFERENCES BETWEEN PEDIATRIC AND ADULT SEPSIS PATHOPHYSIOLOGY
 In adults SVR is almost universally decreased whereas cardiac output (CO) is usually increased so
the result is a distributive shock with hypotension termed warm shock. Clinically these patients have
warm, well-perfused skin, bounding pulses and brisk or flash capillary refill time.
 In children approximately 20% present with signs of warm shock.
 The more common cardiovascular response to severe sepsis in children present in approximately
60% of cases is an increase in SVR as a result of peripheral vasoconstriction
 Redistribution of blood from non essential organs to essential organs & decrease in CO either as a
direct result of impaired cardiac contractility or as a secondary effect of high afterload. This clinical
syndrome is referred to as cold shock.
Peripheral pulses may be weak or absent, the extremities may appear cool, pale or cyanotic and
capillary refill time is delayed.
 An important distinction is that BP is usually maintained and may be supra normal in children with cold
shock.
 Occasionally, both CO and SVR may be decreased in a child with septic shock. This situation may
result in a clinical syndrome that is difficult to classify as either strictly warm or cold shock.

21. investigations
 For sepsis – essential investigations –
 CBC with platelet count
 Smear for malarial parasite & rapid malarial antigen test
 Blood culture
 Urine R/M & C/S- process for culture in 1 hr of collection
 Cxray
 USG abdomen
 CRP & if available Procalcitonin
 CSF analysis – shold be evaluated in half an hour of
collection
 Tissue/ pus culture
 Seological test like NS 1 / widal test

22. Lab anomalies
In septic shock
 RBS
 Blood gas
 ScvO2
 Complete blood count with differential (including platelet count)
 Peripheral smear – to see microangiopathic changes
 Blood lactate – Elevation of blood lactate (>3.5 mmol/L) obtained by arterial puncture or from an indwelling vascular
cannula
 An observational study of bloodlactate levels in 239 children with SIRS suggest that venous blood lactate >
4 mmol/L at initialpresentation is associated with progression to organ dysfunction at 24 hour
( Scott HF, Donoghue AJ, Gaieski DF, et al. The utility of early lactate testing in undifferentiated pediatric
systemic inflammatory response syndrome Acad Emerg Med 2012; 19:1276)
 Serum electrolytes – Electrolyte disturbances (eg hyponatremia, hyperkalemia, hypokalemia and hypophosphatemia)

 Serum calcium – Hypocalcemia (ionized calcium <1.1 mmol/L) may affect myocardial function and
vascular tone and should be corrected if present. If serum calcium is abnormal, serum phosphorus and
magnesium should also be measure
 Blood urea nitrogen and serum creatinine – Elevation in blood urea nitrogen may indicate dehydration.
 Serum creatinine ≥2 times upper limitof normal for age or twofold increase in baseline creatinine defines renal d
ysfunction in the setting of sepsis.

23.  Serum total bilirubin and alanine aminotransferase – Total bilirubin ≥4 mg/dL (not applicable to
newborn) or alanine aminotransferase (ALT) >2 times upper limit of normal for age indicates liver
dysfunction in the setting of sepsis.
 Prothrombin time (PT), partial thromboplastin time (aPTT), international normalized ratio (INR)
 Fibrinogen and D dimer – Decreased fibrinogen and increased D dimer support the presence of a
consumptive coagulopathy and DIC.
 Blood culture – Given the high prevalence of bacterial bloodstream infections in children with sepsis,
blood cultures should be obtained in all patients, preferably before antibiotics are administered.
 Urinalysis – presence of bacteria, nitrites or pyuria suggests a urinary tract infection.
 Urine culture – Urinary tract infection is a common source of infection in children with sepsis and
catheterized urine cultures should be obtained in all patients, preferably before antibiotic administration.
 Other cultures – cerebrospinal fluid [CSF], wound culture, aspirated fluid from an
abscess collection, and/or viral or fungal cultures should be obtained as indicated by clinical findings.
 For some infections (eg herpes simplex virus, enterovirus, influenza)
other diagnostic testing (eg viral culture, polymerase chain reaction, rapid immunoassay antigen test or
direct and immunofluorescent antibody staining) may be helpful to establish the source of infection.

24. Soluble trigger
Receptor
On myeloid cells

25.  Inflammatory biomarkers,such as Creactive protein and procalcitonin may be useful
in selected cases but routine testing is not currently recommended
(Marshall JC, Reinhart K, International Sepsis Forum. Biomarkers of sepsis. Crit Care M
ed 2009; 37:229)
 CRP and procalcitonin may be helpful in children with no source of infection,
in predicting bacterial infection in patients with fever and neutropenia.
( LuacesCubells C et al. Procalcitonin to detect invasive bacterial infection in nontoxic
appearing infants with fever without apparent source in the emergency department. Pedi
atricinfect Dis J 2012; 31:645 )
Molecular methods to identify bacterial and viral infections include polymerase chain
reaction and detection of
bacterial 16S ribosomal ribonucleic acid (RNA) genes or host RNA signatures.

26. Imaging
 Children with tachypnea, rales, wheezing, hypoxemia, or white blood cell
count greater than20,000/mm warrant a chest radiograph to assess for
bronchopneumonia, pulmonary edema, and heart size.
 Cardiomegaly suggests fluid overload or congenital heart disease.
 Other imaging as (CT)of the head may be necessary in the patient with
evidence of coagulopathy and altered mental status to
evaluate for intracranial hemorrhage.
 Ultrasound or computed tomography of the abdomen may be indicated
to evaluate for intraabdominal abscess.

29. TREATMENT

30. Prior steroid use, purpura fulminans, HIV,
chronic pituitary or adrenal abnormality –
2 mg/kg loading f/b 2 mg/kg/day either
6 hrly or continuous infusion

31. Rule out & correct
Pericardial effusion
Pneumothorax
Hypoadrenalism
Hypothyroidsm
Ongoing blood loss
Intra abdominal catastrophe
Necrotic tissue
Persistent Catecholamine resistant shock

34. Surving Sepsis International Guidelines for
Management of Severe Sepsis and Septic Shock

35. Source Control
 A specific anatomical diagnosis of infection requiring consideration for emergent source control be
sought and intervention be undertaken for source control within the first 12 hr after the diagnosis is
made.
 When infected peri pancreatic necrosis is identified as a potential source of infection, definitive
intervention is best delayed until adequate demarcation of viable and nonviable tissues has occurred.
 Effective intervention associated with the least physiologic insult should be used eg percutaneous
rather than surgical drainage of an abscess.
 If intravascular access devices are a possible source of severe sepsis or septic shock, they should be
removed promptly after other vascular access has been established.
Infection Prevention
 Selective oral decontamination and selective digestive decontamination like oral chlorhexidine
gluconate be used as a form of oropharyngeal decontamination to reduce the risk of ventilator
associated pneumonia in ICU patients with severe sepsis

36. <10000 prophylactic, <20000 with risk of bleeding, >50000 for surgery or invasive procedure
Fresh frozen plasma not be used to correct laboratory clotting abnormalities in the absence of bleeding or planned invasive procedures

37. High PEEP, low TV @6ml/kg, pleateau pressure less than 30, Recruitment maneovur like prone position in Pao2/Fio2
less than 100, Head end elevation to 30 to 45 degree to prevent aspiration & VAP

39. Future prospective in Sepsis

40. Other therapies of sepsis

43. Nutritional supplementation in TRIAL
 Selenium- trace element that is an essential micronutrient
for a variety of biological processes, serving as a cofactor
for thyroid hormone function and antioxidant reduction.
 Its use in sepsis is based on the known reduced
concentrations in septic patients and the association of its
deficiency with increased morbidity and mortality.
 (Heidemann SM, Holubkov R, Meert KL, et al. Baseline
serum concentrations of zinc, selenium, and prolactin in
critically ill children. Pediatr Crit Care Med 2013;14:e202–
6.)

44. Take Home Message
 The initial clinical presentation of sepsis in children may be non-
specific (especially in younger age groups)
 When sepsis is suspected on clinical grounds it is usually best to start
investigations and treatment for sepsis including fluid resuscitation
and to continue with these until sepsis has been excluded
 Progression to organ failure and shock is often rapid so early
recognition and treatment is crucial
 Apart from antibiotics, there are currently no specific treatments of
proved value
 Other treatment after antibiotics is supportive and should be delivered
according to internationally recognised consensus based guidelines