Septic Shock in Pediatrics

E mail: tareqhamed@liv.com Sepsis is defined as a clinical syndrome that complicates severe infection and is associated with the systemic inflammatory response syndrome as well as immune dysregulation. Circulatory decompensation and end-organ dysfunction will be the ultimate end if sepsis is not properly managed. In this syndrome, tissues remote from the original insult display the cardinal signs of inflammation, including vasodilation, increased microvascular permeability and leukocyte accumulation. Recently pediatric mortality from severe sepsis and septic shock has markedly decreased because of early recognition, aggressive fluid therapy and early administration of vasoactive agents in addition to antibiotics.


DEFINITION
Septic shock refers to sepsis with cardiovascular dysfunction that persists despite the administration of ≥40 mL/kg of isotonic fluid in one hour [1].
Pediatric sepsis is generally considered to comprise a spectrum of disorders that result from infection by bacteria, viruses, fungi, or parasites or the toxic products of these microorganisms.Early recognition and intervention clearly improve the outcome for infants and children with conditions that lead to sepsis [2].
The spectrum of sepsis ranges from microbial invasion of the bloodstream or intoxication with early signs of circulatory compromise including tachycardia, tachypnea, peripheral vasodilation, and fever (or hypothermia) to full-blown circulatory collapse with multiple organ dysfunction syndrome (MODS) and death [3].

How can we diagnose septic shock?
A clinical diagnosis of septic shock is made in children who have signs of inadequate tissue perfusion, two or more criteria for the systemic inflammatory response syndrome, and suspected or proven infection [4].Rapid recognition of hemodynamic abnormalities and early suspicion of infection are essential to achieve favorable outcomes.

1-Signs of inadequate tissue perfusion
Seriously ill patients should undergo urgent evaluation for the following signs of impaired perfusion or shock [5]:  Fever. Tachycardia or bradycardia. Decreased peripheral pulses compared with central pulses. Mottled or cool extremities. "Flash" or >3 second capillary refill. Dry mucus membranes, sunken eyes, and decreased urine output. Tachypnea, bradypnea, or apnea  Hypotension. Altered mental status (irritability, anxiety, confusion, lethargy, somnolence, apnea). Hypothermia (especially neonates.

2-Signs of infection
Patients should be simultaneously evaluated for an infectious source to distinguish non-infectious from septic shock.Fever, cough or congestion, dyspnea, hypoxemia, rash, abdominal pain, myalgias, immunocompromising condition (chemotherapy, sickle cell disease, or other known conditions associated with splenic dysfunction or primary immune deficiency), leukocytosis, or leukopenia with thrombocytopenia should raise suspicion for infection.Other factors concerning for specific infections, such as dysuria (urinary tract infection), hematochezia (gastroenteritis), headache and neck stiffness (meningitis), bone or joint inflammation (Staphylococcus aureus), conjunctival suffusion / injection (toxic shock syndrome), ecthyma (Pseudomonas species) and petechiae/purpura (meningococcemia), should also be quickly ascertained.If an infection is suspected or a non-infectious etiology of shock is not clear, current guidelines recommend obtaining blood, urine, and, as indicated, other cultures and administering empiric broad-spectrum antibiotics within one hour of presentation [6].Antibiotic therapy should not be delayed beyond one hour in order to obtain cultures if there is a concern for severe sepsis or septic shock.

3-Systemic inflammatory response syndrome
The systemic inflammatory response syndrome (SIRS) is a widespread inflammatory response that may or may not be associated with infection.

REFRACTORY SEPTIC SHOCK
Fluid-refractory, catecholamine-resistant shock is defined as cardiovascular dysfunction despite at least 60 mL/kg of fluid resuscitation and dopamine ≥10 mcg/kg/min and/or direct-acting catecholamine (epinephrine, norepinephrine).Principles of management for children with refractory septic shock include treatment of reversible etiologies, stress dose corticosteroid therapy for patients with absolute adrenal insufficiency, and combination vasoactive drug therapy targeted to maintaining central venous oxygen saturation ≥70 percent and normalizing blood lactate levels.
Although cardiac index targets are mentioned in previous pediatric septic shock guidelines, evidence of improved outcomes from routine measurement of cardiac index is lacking.If performed, the target range is 3.3 to 6.0 L/min/m2 [19].

Correction of reversible conditions
Pneumothorax, pericardial tamponade, and intraabdominal complications (like, peritonitis or ascites) comprise mechanical causes of shock that can be reversed by chest tube thoracotomy, pericardiocentesis, or abdominal decompression surgery, respectively.Drainage or debridement of infection sites (like, necrotizing fasciitis) or broadening of antimicrobial coverage are additional actions that may be warranted [20].
Is there a rule for extracorporeal membrane oxygenation (ECMO)?American College of Critical Care Medicine (ACCM) suggest that children with persistent catecholamine-resistant shock in whom physiologic targets cannot be attained with fluid repletion, vasoactive infusion, and hormonal therapy; who do not have an immediately reversible cause, such as myocarditis, pneumothorax, or pericardial effusion; and who have a high likelihood of mortality, be evaluated for extracorporeal membrane oxygenation (ECMO) support, if available.If ECMO is not available at the facility in which the child is receiving care then the potential benefits of ECMO must be weighed against the likelihood that the patient can tolerate transfer [21].

What is place of Intravenous immune globulin in management of septic shock?
Adjuvant therapy with intravenous immune globulin (IVIG) has been proposed but evidence for benefit in children with septic shock remains inconclusive.A trial of polyclonal IVIG in 100 children with pediatric sepsis syndrome showed a significant reduction in mortality (28 versus 44 percent), length of stay (six versus nine days), and less progression to complications (8 versus 32 percent) [22].

Is there a rule of Plasma exchange or plasmapheresis in the future?
There has been considerable interest in extracorporeal filtration of circulating inflammatory mediators in sepsis.Although multiple studies in adults have been published on plasma exchange and plasmapheresis in sepsis, most are limited by small sample size at single institutions with considerable variability in the protocols utilized.Thus, current evidence is conflicting as to clinical benefit [23].

PROGNOSIS
Early recognition and management of pediatric severe sepsis and septic shock can be improved through the establishment of institutional care guidelines.
Many Factors are affecting the prognosis of septic shock.The most important are related to the host.Case fatality rates in children with severe sepsis are highest for infants 1 to 12 months of age (approximately 11 percent) and are higher across all age groups for children with comorbidities, especially in children with cancer or human immunodeficiency virus infection (12 to 16 percent) [24].Site of infections is another prognostic factor.Children with endocarditis, central nervous system infection, and primary bacteremia have high case fatality rates (15 to 20 percent) [3].The case fatality rate is lowest for genitourinary tract infections (approximately 4 percent) [25].Microorganism may influence the progression from systemic inflammatory response syndrome to severe sepsis or septic shock and provide predictors of mortality.Case fatality is increased in children with pneumococcal and fungal infections (15 and 13 percent, respectively) [3].Infection with organisms resistant to antibiotics (like, methicillin-resistant Staphylococcus aureus or vancomycin-resistant enterococcus species) is associated with a marked increased mortality from sepsis [26].Mortality increases markedly depending upon the severity of illness in children with sepsis [27].The development of multiple organ dysfunction indicates an increased severity of illness in patients with sepsis and is associated with a higher mortality estimated as 0 to 7 percent for patients with one affected organ system and 20 to 50 percent with two or more failing organ systems [24].Treatment requirements are also important prognostic indicators.The need for multiple vasoactive infusions predicts a poor prognosis [28].