Sepsis In Children

Presented by – Dr Anand Singh (DCH DNB )

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

definitions

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

MODS(multi organ dysfunction )

Presence of altered organ function such that homeostasis cannot be maintained without medical intervention

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

Epidemology

Sepsis is single largest cause of child mortality accounting for more thanhalf 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 neonatesare 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

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 )

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 coagulantAPC & Antithrombin, thus prevents coagulation cascade

Production of PAI 1 which is inhibitor of fibrinolysis

1. Capillary lekage due to endothelial damage2. 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 inflamtorycytokines 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 toCardiovascular insufficiency & MODY & Death

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

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

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 )

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

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

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

Clinical Feature

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.-

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.

DIFFERENCES BETWEEN PEDIATRIC AND ADULT SEPSIS PATHOPHYSIOLOGY

In adults SVR is almost universally decreased whereas cardiac output (CO) is usually increased sothe result is a distributive shock with hypotension termed warm shock. Clinically these patients havewarm, 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 approximately60% 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 adirect 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 andcapillary refill time is delayed.

An important distinction is that BP is usually maintained and may be supra normal in children with coldshock.

Occasionally, both CO and SVR may be decreased in a child with septic shock. This situation mayresult in a clinical syndrome that is difficult to classify as either strictly warm or cold shock.

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 ofcollection

Tissue/ pus culture

Seological test like NS 1 / widal test

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 vascularcannula

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 pediatricsystemic 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 andvascular tone and should be corrected if present. If serum calcium is abnormal, serum phosphorus andmagnesium 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 dysfunction in the setting of sepsis.

Serum total bilirubin and alanine aminotransferase – Total bilirubin ≥4 mg/dL (not applicable tonewborn) or alanine aminotransferase (ALT) >2 times upper limit of normal for age indicates liverdysfunction 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 aconsumptive 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 andcatheterized urine cultures should be obtained in all patients, preferably before antibiotic administration.

Other cultures – cerebrospinal fluid [CSF], wound culture, aspirated fluid from anabscess 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.

Soluble triggerReceptor On myeloid cells

Inflammatory biomarkers,such as Creactive protein and procalcitonin may be usefulin selected cases but routine testing is not currently recommended

(Marshall JC, Reinhart K, International Sepsis Forum. Biomarkers of sepsis. Crit Care Med 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. Pediatricinfect Dis J 2012; 31:645 )

Molecular methods to identify bacterial and viral infections include polymerase chainreaction and detection of

bacterial 16S ribosomal ribonucleic acid (RNA) genes or host RNA signatures.

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.

TREATMENT

Prior steroid use, purpura fulminans, HIV, chronic pituitary or adrenal abnormality –2 mg/kg loading f/b 2 mg/kg/day either6 hrly or continuous infusion

Rule out & correct

Pericardial effusion

Pneumothorax

Hypoadrenalism

Hypothyroidsm

Ongoing blood loss

Intra abdominal catastrophe

Necrotic tissue

Persistent Catecholamine resistant shock

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

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

<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

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

Future prospective in Sepsis

Other therapies of sepsis

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.)

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