Chapter 176 Sepsis, Septic Shock, and Systemic Inflammatory Response Syndrome

Maria Annette Enrione Keith R. Powell Despite advances in vaccines and pharmacologic agents, infection triggering sepsis that can progress to septic shock and ultimately death continues to be a major pediatric problem. The systemic inflammatory response syndrome (SIRS) is an inflammatory cascade that is initiated by the host in response to infection with bacteria, rickettsiae, fungi, viruses, and protozoa. This inflammatory cascade occurs when the host defense system does not adequately recognize or clear the infection. SIRS can also occur from a number of noninfectious etiologies ( Table 176-1 ). Sepsis is defined as SIRS resulting from a suspected or proven infection. The clinical spectrum of sepsis begins when a systemic infection (e.g., bacteremia, fungemia, viremia) or localized infection (e.g., meningitis, pneumonia, pyelonephritis) progresses from sepsis to severe sepsis (the presence of sepsis combined with organ dysfunction), septic shock (severe sepsis plus the persistence of hypoperfusion or hypotension for >1 hr despite adequate fluid resuscitation or a requirement for inotropic agents or vasopressors), multiple organ dysfunction syndrome (MODS), and ultimately death ( Table 176-2 ). This is a complex clinical problem, and with early recognition and treatment there is a high likelihood of a good outcome.

TABLE 176-1 -- Differential Diagnosis of SIRS INFECTION Bacteremia or meningitis (Streptococcus pneumoniae, Haemophilus influenzae type b, Neisseria meningitidis, group A streptococcus, S. aureus) Viral illness (influenza, enteroviruses, hemorrhagic fever group, HSV, RSV, CMV, EBV) Encephalitis (arboviruses, enteroviruses, HSV) Rickettsiae (Rocky Mountain spotted fever, Ehrlichia, Q fever) Syphilis Vaccine reaction (pertussis, influenza, measles) Toxin-mediated reaction (toxic shock, staphylococcal scalded skin syndrome) CARDIOPULMONARY Pneumonia (bacteria, virus, mycobacteria, fungi, allergic reaction) Pulmonary emboli Heart failure Arrhythmia Pericarditis Myocarditis METABOLIC-ENDOCRINE

Adrenal insufficiency (adrenogenital syndrome, corticosteroid withdrawal) Electrolyte disturbances (hyponatremia or hypernatremia; hypocalcemia or hypercalcemia) Diabetes insipidus Diabetes mellitus Inborn errors of metabolism (organic acidosis, urea cycle, carnitine deficiency, mitochondrial disorders) Hypoglycemia Reye syndrome GASTROINTESTINAL Gastroenteritis with dehydration Volvulus Intussusception Appendicitis Peritonitis (spontaneous, associated with perforation or peritoneal dialysis) Necrotizing entercolitis Hepatitis Hemorrhage Pancreatitis HEMATOLOGIC Anemia (sickle cell disease, blood loss, nutritional) Methemoglobinemia Splenic sequestration crisis Leukemia or lymphoma Hemophagocytic syndromes NEUROLOGIC Intoxication (drugs, carbon monoxide, intentional or accidental overdose) Intracranial hemorrhage Infant botulism Trauma (child abuse, accidental) Guillain-Barr syndrome Myasthenia gravis OTHER

Anaphylaxis (food, drug, insect sting) Hemolytic-uremic syndrome Kawasaki disease Erythema multiforme Hemorrhagic shockencephalopathy syndrome Poisoning Toxic envenomation Macrophage activation syndrom CMV, cytomegalovirus; EBV, Epstein-Barr virus; HSV, herpes simplex virus; RSV, respiratory syncytial virus; SIRS, systemic inflammatory response syndrome.

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. 2. Core temperature >38.5C or <36C (rectal, bladder, oral, or central catheter) 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 0.54 hr; OR in children <1 yr old persistent bradycardia over 0.5 hr (mean heart rate <10th percentile for age in absence of vagal stimuli, blocker drugs, or congenital heart disease) Respiratory rate >2 SD above normal for age or acute need for mechanical ventilation not related to neuromuscular disease or general anesthesia Leukocyte count elevated or depressed for age (not secondary to chemotherapy) or >10% immature neutrophils

3. 4.

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 percentile for age, systolic blood pressure <2 SD below normal for age 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 mL/kg/hr Prolonged capillary refill 5 sec Core to peripheral temperature gap >3C 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. Adapted from Goldstein B, Giroir B, Randolph A: International pediatric sepsis consensus conference: Definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care 2005;6(1):28. Copyright 2005, Lippincott Williams & Wilkins.

ETIOLOGY.

Sepsis may develop as a complication of a localized infection or may follow colonization and mucosal invasion by virulent pathogens (see Table 176-1 ). Children 3 mo to 3 yr of age are at risk for occult bacteremia that will occasionally progress to sepsis (see Chapter 175 ). Patients at risk for sepsis include infants, children with serious injuries, children on chronic antibacterial therapy, malnourished children, and children with chronic medical problems. Also, children who are immune suppressed (transplant recipients on immunosuppressive regimens, patients on chemotherapeutic agents or corticosteroids, patients with acquired or congenital immune deficiencies) are at an increased risk for complications from infection, including sepsis and septic shock. 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. Rickettsia rickettsii causing Rocky Mountain spotted fever occurs in endemic areas and can lead to septic shock. Nosocomial (hospital-acquired) infections pose a special risk to immunocompromised patients (see Chapter 177 ). Intravenous and arterial catheters, urinary catheters, and endotracheal tubes are portals for the development nosocomial

infections (see Chapter 178 ). Invasive procedures can also lead to nosocomial infections. 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. Polymicrobial sepsis occurs in high-risk patients and is associated with catheters, gastrointestinal disease, neutropenia, and malignancy. Unusual pathogens should be suspected in patients who have traveled or been exposed to products or people from distant lands or who are immunocompromised secondary to malignancy, T- or B-cell defects, or asplenia (acquired or congenital). Pseudobacteremia may be associated with contaminated heparin flush solutions, intravenous solutions, albumin, cryoprecipitate, and infusion equipment. Contaminants include water-borne organisms such as Burkholderia cepacia, Pseudomonas aeruginosa, and Serratia.
PATHOGENESIS.

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. Microcirculatory dysfunction results in endothelial injury, release of vasoactive substances, changes in cardiovascular tone, mechanical obstruction of the capillary beds from aggregation of cellular elements, and activation of the complement system. At the cellular level there is decreased oxidative phosphorylation secondary to decreased oxygen delivery, anaerobic metabolism secondary to decreased adenosine triphosphate (ATP), glycogen depletion, lactate production, increased cytosolic calcium, activation of membrane

phospholipases (further depleting ATP), and release of fatty acids with prostaglandin formation. The inflammatory cascade ( Fig. 176-1 ) is initiated by toxins or superantigens. Endotoxin (a lipopolysaccharide), mannose, and glycoprotein components of the cell wall of gram-negative bacteria as well as fungi and yeast bind to macrophages leading to activation and expression of inflammatory genes. Superantigens or toxins associated with gram-positive bacteria, mycobacteria, and viruses activate circulating lymphocytes and initiate an inflammatory mediator cascade.

Figure 176-1 Hypothetical pathophysiology of the septic process.

Biochemical responses include the production of arachidonic acid metabolites, release of myocardial depressant factors, release of endogenous opiates, activation of the complement

system, as well as the production and release of many other mediators. Arachidonic acid metabolites include (1) thromboxane A2, which causes vasoconstriction and platelet aggregation; (2) prostaglandins, such as PGF 2, which causes vasoconstriction, and PGI2, which causes vasodilation; and (3) leukotrienes that cause vasoconstriction, bronchoconstriction, and increased capillary permeability. Myocardial depressant factors, tumor necrosis factor- (TNF), and some of the interleukins cause myocardial depression not only via direct myocardial injury but also by an intracardiac increase in inducible nitric oxide synthase. Endogenous opiates, including -endorphin, decrease sympathetic activity, decrease myocardial contractility, and cause vasodilation. Activation of the complement system leads to release of vasoactive mediators that increase capillary permeability, cause vasodilation, and cause activation and aggregation of platelets and granulocytes. Endogenous mediators of sepsis continue to be identified and currently include TNF, interleukin 1 (IL-1), IL-2, IL-4, IL-6, IL-8, platelet activating factor (PAF), interferon-, eicosanoids (leukotrienes B4, C4, D4, and E4; thromboxane A2; prostaglandins E2 and I2), granulocyte-macrophage colony-stimulating factor, endothelium-derived relaxing factor, endothelin-1, complement fragments C3a and C5a, toxic oxygen radicals, proteolytic enzymes from polymorphonuclear neutrophils, platelets, transforming growth factor-, vascular permeability factor, macrophage-derived procoagulant and inflammatory cytokine, bradykinin, thrombin, coagulation factors, fibrin, plasminogen activator inhibitor (PAI-1), myocardial depressant substance, -endorphin, heat shock proteins, and adhesion molecules (endothelin-derived adhesion molecule [E-selectin]; intercellular adhesion molecule-1 [ICAM]; vascular adhesion molecule-1 [VCAM]). 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 proinflammatory 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 -endorphin, and production of myocardial nitric oxide. In addition to treating the underlying infection, therapies to augment the host defense, block trigger events, prevent leukocyte-endothelial interaction, and inhibit vasoactive substances, cytokines or lipid mediators are being investigated. To date, the results of clinical trials investigating drugs targeting the mediators of SIRS have been disappointing. Trials have been conducted with anti-endotoxin antibodies, antioxidant compounds, an IL-1 receptor antagonist, IL-1 antibodies, bradykinin-receptor antibodies, cyclo-oxygenase inhibitors, thromboxane antagonists, PAF antagonists, inhibitors of leukocyte-adhesion molecules, nitric oxide antagonists, anti-TNF antibody, bactericidal permeability-increasing protein, and recombinant human activated protein C. Recombinant human activated protein C (drotrecogin-) studies have shown improvement in the 28-day survival in adults, but enrollment in a pediatric trial was closed early because of an unfavorable risk-benefit ratio

particularly in neonates. The best treatment is early recognition, early antimicrobial therapy, and early goal-directed therapy.
CLINICAL MANIFESTATIONS.

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 standard deviations below the mean for age) is a late finding in children with sepsis, it is not a criteria for the diagnosis of shock in infants and young children (see Table 176-2 ). 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. Cutaneous lesions seen in septic patients include petechiae, diffuse erythema, ecchymoses, ecthyma gangrenosum, and symmetric peripheral gangrene. Jaundice can be seen either as a sign of infection or as a result of MODS. The patient may also have evidence of focal infection such as meningitis, pneumonia, arthritis, cellulitis, or pyelonephritis.
DIAGNOSIS.

The diagnosis of sepsis requires SIRS (see Table 176-2 ) in the presence of proven infection or a clinical picture consistent with infection. An infectious etiology should be sought by culturing clinically appropriate specimens taken from body fluids (blood, urine, cerebrospinal fluid, abscesses, peritoneal fluid, etc.). Infectious disease and intensive care consults are necessary. Cultures take time for incubation and are not always positive. Additional evidence to identify an infectious etiology as the cause of SIRS includes physical examination findings, imaging (chest radiograph with evidence of pneumonia), presence of white cells in normally sterile body fluids, and suggestive rashes such as petechiae and purpura. Affected children should be admitted to an intensive care unit where continuous, close invasive monitoring can be performed, including central venous pressure and arterial blood pressure (see Chapter 68 ).
LABORATORY FINDINGS.

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 Dhle 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. Renal and liver function may be abnormal if the

patient develops MODS. Patients with acute respiratory distress syndrome or pneumonia will have impaired oxygenation (decreased PaO2) and ventilation (increased Paco2). Examination of infected body fluids may reveal neutrophils and bacteria.
TREATMENT.

Early administration of antimicrobial agents is associated with a reduction of mortality. The choice of antimicrobial agents is dependent on the predisposing risk factors and the clinical situation. Bacterial resistance patterns in the community should also be considered when selecting optimal antimicrobial therapy. 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 gramnegative 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 ).

TABLE 176-3 -- Appropriate Antibiotics for Pediatric Sepsis Neonate Ampicillin plus aminoglycoside or cefotaxime Add vancomycin if nosocomial infection Add acyclovir if suspect herpes simplex virus Child Cefotaxime or ceftriaxone Add vancomycin for meningitis or in areas of high staphylococcal or pneumococcal resistance to methicillin or cefotaxime, respectively Immunocompromised patient or nosocomial infection Vancomycin + antipseudomonal antibacterial agent Ceftazidime or cefepime Aminoglycoside Penicillin b-lactamase inhibitor combination (ticarcillin/clavulanic, piperacillin/tazobactam) Carbapenem (imipenem or meropenem)

Toxic shock syndrome

Penicillin plus clindamycin Vancomycin if methicillin Staphylococcus aureus is suspected Add doxycycline to above regimens Add clindamycin or metronidazole to above regimens

Tick-endemic areas Suspected anaerobic infections

SUPPORTIVE CARE.

A recommended stepwise approach to pediatric septic shock is based on the consensus statement of the American College of Critical Care Medicine (ACCCM)/Society for Critical Care Medicine Task Force Committee Members ( Fig. 176-2 ).

Figure 176-2 American College of Critical Care Medicine and American Heart Association clinical parameters for the hemodynamic support of pediatric patients with septic shock. PICU, pediatric intensive care unit; SVC O 2 sat, superior vena cava oxygen saturation; MAP, mean arterial pressure; CVP, central venous pressure; CI, cardiac index; ECMO, extracorporeal membrane oxygenation. (From Carcillo JA, Fields AI, Task Force Committee Members: Clinical practice parameters for hemodynamic support of pediatric and neonatal patients with septic shock. Crit Care Med 2002;30(6):13651378. Copyright 2002, Lippincott Williams & Wilkins.)

Early goal-directed therapy is the recommended treatment approach for patients with septic shock. Rapid, aggressive resuscitation with fluids and catecholamines is associated with a reduction in mortality. Every hour of inadequate resuscitation is associated with an increased mortality risk of 40%. Fluid resuscitation of 60 mL/kg is associated with improved survival without an increased incidence of pulmonary edema. Fluid resuscitation in increments of 20 mL/kg should be titrated to normalize heart rate (using age-based heart rates), urine output (to at least 1 mL/kg/hr), capillary refill (<2 sec), and mental status. Since hypotension is a late ominous finding, blood pressure is not a reliable end-point for assessing resuscitation. Fluid resuscitation may sometimes require as much as 100200 mL/kg. Although the type of fluid (crystalloid vs colloid) is still an area of debate, there is no question that fluid resuscitation is essential to survival from septic shock (see Chapter 68 ). Other fluids to consider include blood products. Oxygen delivery is primarily dependent on the hemoglobin concentration. Thus, maintaining the hemoglobin at 10 g/dL is a reasonable goal in the absence of data from randomized clinical trials. Correction of coagulopathy with fresh frozen plasma, cryoprecipitate, and platelet transfusions should be considered, especially if the patient has active bleeding. Evidence suggests that infants and children tend to have low cardiac output with vasoconstriction and that progressive myocardial dysfunction is associated with a higher mortality rate. Thus, goal-directed therapy includes the use of vasopressors and inotropic agents in an attempt to maintain a normal cardiac index. Dopamine is the initial choice for fluid-refractory shock. In dopamine-resistant shock, epinephrine or norepinephrine should be considered. Dobutamine is useful in cases where cardiac output is low. In patients with high systemic vascular resistance and epinephrine-resistant low cardiac output, the use of vasodilators such as nitroprusside or type III phosphodiesterase inhibitors (milrinone) may reverse shock. Arginine vasopressin may be useful in norepinephrine-resistant shock because it does not require the receptor for action. Metabolic status should be maintained. Thus, electrolytes should be monitored closely and corrected as needed. Hypoglycemia should be treated with 0.51.0 g/kg of glucose. Hypocalcemia, which can contribute to cardiac dysfunction, should be treated with 1020 mg/kg of calcium chloride through a central venous catheter. Studies have shown that 50% of children in the intensive care unit have a relative or absolute adrenal insufficiency. Thus, use of stress dose corticosteroids (hydrocortisone 50 mg/kg bolus followed by 50 mg/kg/day) for adrenal insufficiency should be considered, especially if shock is not responsive to catecholamines and fluid resuscitation. Lower dose therapy may also be effective but requires further study. All patients with adrenal suppression secondary to

chronic steroid therapy, including patients with asthma, rheumatic diseases, and inflammatory bowel disease, as well as patients with known disorders of the hypothalamicpituitary axis (hypopituitarism, congenital adrenal hyperplasia) should receive stress dose corticosteroids. Other therapies, including respiratory support and renal replacement therapy, should be used as clinically appropriate. Lung protective strategies (use of positive end-expiratory pressure, low tidal volume ventilation [68 mL/kg] plateau pressures less than 30 cm of water, and Fio2 less than 60%) should be used in patients who have developed acute respiratory distress syndrome or require mechanical ventilation, because overdistended lungs can generate systemic cytokines, worsening the inflammatory cascade. Renal replacement therapy may be useful in children with anuria or oliguria and severe fluid overload. Extracorporeal membrane oxygenation may be considered in selected patients with refractory septic shock. Monitoring patients with septic shock should minimally include central venous pressure, arterial blood pressure, pulse oximetry, and hourly urine output. Other clinical parameters that should be monitored include heart rate, capillary refill, and mental status. Superior vena cava oxygen saturation may be an indicator of adequate resuscitation. A superior vena cava oxygen saturation of >70% in the 1st 6 hours after shock resuscitation has been associated with improved outcome. There is not enough information to determine whether or not cardiac echocardiography, pulmonary arterial catheterization, and gastric tonography should be used to direct therapy in patients with septic shock. Resuscitation goals include capillary refill <2 sec, normal pulses with no differential between central and peripheral pulses, warm extremities, urine output of >1 mL/kg/hr, normal mental status, and normal blood pressure for age.
PROGNOSIS.

The mortality rate for septic shock depends on the initial site of infection, the bacterial pathogen, the presence of MODS, and the host immune response. Severe sepsis remains one of the leading causes of death in children. Recent outcome data show an improvement in neonatal and pediatric sepsis, with mortality rates around 10%. Infants, especially low birth weight infants, and children with chronic medical problems are at highest risk for developing severe sepsis. Pediatric patients who have undergone bone marrow transplantation have an increased rate of mortality compared to other patients with septic shock. Furthermore, patients who survive septic shock demonstrate an improvement in cardiac indices with therapy as compared with nonsurviving patients. Severe sepsis has an estimated cost of $1.9 billion nationally per year. For children, the mean length of stay was 31 days, with a cost of $40,600. For infants, the mean length of stay was 53 days, with a cost of $56,600. The incidence of severe sepsis is highest among infants (5.2/1,000) and lowest among 514 year olds (0.2/1,000).
PREVENTION.

Immunization with the conjugate H. influenzae type b and S. pneumoniae vaccines is recommended for all infants (see Chapter 170 ). High-risk patients should also receive recommended immunizations. Penicillin prophylaxis to prevent pneumococcal infection is recommended for patients with splenic dysfunction (e.g., sickle cell disease) and those who are asplenic (acquired or congenital). Antibiotic prophylaxis is recommended for household

and other close contacts of patients with invasive N. meningitidis (see Chapter 190 ) or H. influenzae type b disease (see Chapter 192 ). There are recommended measures for prevention of nosocomial infections (see Chapter 178 ) and infection and sepsis in immunocompromised patients (see Chapter 177 ) and neonates (see Chapter 109 ). Email to Colleague Print Version