CHILD SEPSIS - NELSON TEXTBOOK OF PEDIATRICS 18º

TABLE 176-2 -- International Consensus Definitions for Pediatric Sepsis

Infection: Suspected or proven infection or a clinical syndrome associated with high probability of infection

SIRS: 2 out of 4 criteria, 1 of which must be abnormal temperature or abnormal leukocyte count 1. Core temperature >38.5°C or <36°c> 2. Tachycardia: mean heart rate >2 SD above normal for age in absence of external stimuli, chronic drugs or painful stimuli; OR unexplained persistent elevation over 0.5–4 hr; OR in children <1>β blocker drugs, or congenital heart disease) 3. Respiratory rate >2 SD above normal for age or acute need for mechanical ventilation not related to neuromuscular disease or general anesthesia 4. Leukocyte count elevated or depressed for age (not secondary to chemotherapy) or >10% immature neutrophils

Sepsis: SIRS plus a suspected or proven infection

Severe Sepsis: Sepsis plus 1 of the following 1. Cardiovascular organ dysfunction defined as Despite >40 mL/kg of isotonic intravenous fluid in 1 hr Hypotension <5th> OR Need for vasoactive drug to maintain blood pressure OR 2 of the following Unexplained metabolic acidosis: base deficit >5 mEq/L Increased arterial lactate >2 times upper limit of normal Oliguria: urine output <0.5> Prolonged capillary refill 5 sec Core to peripheral temperature gap >3°C 2. Acute respiratory distress syndrome (ARDS) as defined by the presence of a Pao2/FiO2 ratio ≤300 mm Hg, bilateral infiltrates on chest radiograph, and no evidence of left heart failure OR Sepsis plus 2 or more organ dysfunctions (respiratory, renal, neurologic, hematologic, or hepatic) Septic Shock: Sepsis plus cardiovascular organ dysfunction as defined above Multiple Organ Dysfunction Syndrome (MODS): Presence of altered organ function such that homeostasis cannot be maintained without medical intervention SIRS, systemic inflammatory response syndrome; SD, standard deviation.

The infectious agents associated with sepsis in pediatric patients vary with the patient's age and immune status. In the neonatal age group, group B streptococcus, Escherichia coli, Listeria monocytogenes, enteroviruses, and herpes simplex virus are the pathogens most commonly associated with sepsis. In older children Streptococcus pneumoniae, Neisseria meningitidis, and Staphylococcus aureus (methicillin-sensitive or resistant) are more common. Toxic shock syndrome from group A streptococcus or S. aureus can also be seen in older children

Infections with gram-negative bacteria (e.g., Escherichia coli, Pseudomonas, Acinetobacter, Klebsiella, Enterobacter, Serratia) and fungi (e.g., Candida, Aspergillus) most often occur in immunocompromised and hospitalized patients colonized with these organisms.

Shock is a state of circulatory dysfunction that occurs from (1) decreased cardiac output and/or maldistribution of regional blood flow and (2) increased metabolic demands with or without impaired oxygen utilization at the cellular level despite adequate oxygen delivery (see Chapter 68 ). Cardiac output may be high, low, or normal. The body has compensatory mechanisms to maintain blood pressure through increased heart rate and peripheral vasoconstriction. Hypotension, a late finding in infants and children, occurs when the compensatory mechanisms are failing and cardiorespiratory arrest is imminent.

Septic shock is a combination of the three classic types of shock: hypovolemic, cardiogenic, and distributive. Hypovolemia from intravascular fluid losses occurs through capillary leak. Cardiogenic shock results from the myocardial-depressant effects of sepsis. Distributive shock is the result of decreased systemic vascular resistance. The degree to which a patient will exhibit each of these responses is variable. Warm shock occurs in some patients with increased cardiac output and decreased systemic vascular resistance. Cold shock occurs in other patients with decreased cardiac output and elevated systemic vascular resistance. In both cases, perfusion to major organ systems may be compromised. Recent data suggest that, unlike adults in septic shock who present with vasodilation and high cardiac output, newborns and children may have fluid refractory shock and develop progressive myocardial dysfunction.

It is important to distinguish between the infection and the host response to the infection, the inflammatory response. The host's immune response, through the actions of the cellular and humoral immune systems, and the reticular endothelium system, prevents the body from developing sepsis in response to breaches in the host defense system. However, this host immune response produces an inflammatory cascade of highly toxic mediators, including hormones, cytokines, and enzymes. If this inflammatory cascade is uncontrolled, SIRS occurs with subsequent organ and cellular dysfunction from derangement of the microcirculatory system

The clinical manifestations of sepsis and shock are mediated through the inflammatory cascade. Hypovolemia, cardiac and vascular failure, acute respiratory distress syndrome, insulin resistance, decreased CYP450 activity (decreased steroid synthesis), coagulopathy, and unresolved or secondary infection are all results of the inflammatory cascade. TNF and other inflammatory mediators increase vascular permeability, leading to diffuse capillary leak, decreased vascular tone, and, at the microcirculatory level, an imbalance between perfusion and metabolic demands of the tissue. TNF and IL-1 stimulate the release of pro-inflammatory and anti-inflammatory mediators causing fever and vasodilatation. Arachidonic acid metabolites lead to the development of fever, tachypnea, ventilation-perfusion abnormalities, and lactic acidosis. Nitric oxide, released from the endothelium or inflammatory cells, is a major contributor to hypotension. Myocardial depression is caused by myocardial depressant factors, TNF, and some interleukins through direct myocardial injury, depleted catecholamines, increased β-endorphin, and production of myocardial nitric oxide.

The initial signs and symptoms of sepsis include alterations in temperature regulation (hyperthermia or hypothermia), tachycardia, and tachypnea. In the early stages (hyperdynamic phase), the cardiac output increases in an attempt to maintain adequate oxygen delivery to meet the increased metabolic demands of tissues. As sepsis progresses, cardiac output falls in response to the effects of numerous mediators. Although hypotension (systolic arterial pressure <2 style="background: yellow none repeat scroll 0% 0%; -moz-background-clip: border; -moz-background-origin: padding; -moz-background-inline-policy: continuous;">Other signs of poor cardiac output include delayed capillary refill, diminished peripheral and central pulses, cool extremities, and decreased urine output. Alterations in mental status, including confusion, agitation, lethargy, anxiety, obtundation, or coma, can also be signs of poor cardiac output. Capillary leak develops from altered vascular permeability. Lactic acidosis occurs as shock progresses and is the consequence of increased tissue production and decreased hepatic clearance

Dx: consist in prove an infection

Laboratory findings often include evidence of hematologic abnormalities and electrolyte disturbances. Hematologic abnormalities include thrombocytopenia, prolonged prothrombin and partial thromboplastin times, reduced serum fibrinogen levels and elevated fibrin split products, and anemia. Also, elevated neutrophil and increased immature forms (bands, myelocytes, promyelocytes), vacuolation of neutrophils, toxic granulations, and Döhle bodies can be seen with infection. Neutropenia is an ominous sign of overwhelming sepsis. Electrolyte abnormalities include hyperglycemia as a stress response or hypoglycemia if glycogen reserves are exhausted. Other electrolyte abnormalities include hypocalcemia, hypoalbuminemia, metabolic acidosis, and low serum bicarbonate. Lactic acidosis can occur if there is significant anaerobic metabolism.

Broad-spectrum bactericidal synergistic antimicrobial agents should be promptly administered to the patient in septic shock. The choice of antimicrobial agents depends on the specific predisposing risk factors ( Table 176-3 ). Neonates should be treated with ampicillin plus cefotaxime or gentamicin. Acyclovir should be added if herpes simplex virus is suspected. Community-acquired infections with N. meningitidis, S. pneumoniae, and Haemophilus influenzae can be treated empirically with a 3rd generation cephalosporin (ceftriaxone or cefotaxime) unless resistant S. pneumoniae or S. aureus is prevalent, which requires the addition of vancomycin. If an intra-abdominal process is suspected, anaerobic coverage should be included with agents such as metronidazole or clindamycin. Nosocomial sepsis should be treated with a 3rd or 4th generation cephalosporin or an extended gram-negative spectrum penicillin (e.g., piperacillin-tazobactam) plus an aminoglycoside. Vancomycin should be added to the regimen if the patient has an indwelling medical device (see Chapter 178 ) and gram-positive cocci are isolated from the blood, if methicillin-resistant S. aureus infection is suspected, and as empiric coverage for S. pneumoniae in patients with meningitis. Empirical use of amphotericin B to treat fungal infections should be considered for selected immunocompromised patients (see Chapter 177 ).

Nelson Textbook of Pediatrics,
18th