Infection is problematic because it affects many patients (adults and children), is a major cause of death in ICUs worldwide, and uses a large amount of hospital resources.<sup>22 Brun-Buisson C., Doyan F., Carlet J. , e al. Incidence, risk factors, and outcome of severe sepsi and septic shock in adults JAMA 1995 ;  274 : 968-974

Cliccare qui per andare alla sezione Riferimenti, 117 Pearse R.G., Sauer P.J.J. Exchange transfusion in treatment of severe infections in newborn of sclerema neonatorum Arch Dis Child 1978 ;  53 : 262

Cliccare qui per andare alla sezione Riferimenti</sup> The mortality rate among patients with septic shock varies but approximates 40%<sup>15 Bone R.C. Pathophysiology of sepsis Ann Intern Med 1991 ;  115 : 457-469

Cliccare qui per andare alla sezione Riferimenti, 122 Redl-Wenzl E.M., Armbruster C., Edelmann G. , e al. The effects of norepinephrine on hemodynamics and renal function in severe septic shock states Intensive Care Med 1993 ;  19 : 151-154  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> in infected patients admitted to ICUs. Because of the large number of adults dying of sepsis (250,000 each year in the United States alone),<sup>153 Wheedon D., Shore D.R., Lincoln C. Continuous monitoring of pulmonary artery pressure after cardiac surgery in infants and children J Cardiovasc Surg 1981 ;  22 : 307-311

Cliccare qui per andare alla sezione Riferimenti</sup> many resources are expended. Children are physiologically different from adults, but nonetheless many similarities exist with respect to the response to septic shock.

The term systemic inflammatory response syndrome (SIRS) was proposed by the American College of Chest Physicians and Society of Critical Care Medicine to describe the nonspecific inflammatory process occurring in adults after trauma, infection, burns, pancreatitis, and other diseases. The criteria developed for use in adults<sup>16 Bone R.C., Balk R.A., Cerra F.B. , e al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis Chest 1992 ;  101 : 1644-1655  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> have been modified for use in children.<sup>75 Jenkins J.K., Carey P.D., Byrne K. , e al. Sepsis-inducted lung injury and effects of ibuprofen pretreatment: Analysis of early alveolar events via repetitive bronchoalveolar lavage Am Rev Respir Dis 1991 ;  143 : 155-161

Cliccare qui per andare alla sezione Riferimenti</sup> SIRS encompasses several stages of infection, from sepsis to sepsis syndrome, early septic shock, and refractory shock, which can lead to multiple organ dysfunction and death.<sup>130 Sander A., Armbruster W., Sander B. , e al. Hemofiltration increases IL-6 clearance systemic inflammatory response syndrome but does not alter IL-6 and TNF-⍺ plasma concentrations Intensive Care Med 1997 ;  23 : 878-884  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup>

Sepsis is a systemic response to infection. Evidence of bacteremia or an infective focus is not required for diagnosis. When sepsis is accompanied by altered organ perfusion, as manifested by hypoxemia, increased plasma levels of lactate, oliguria, or acute changes in mental status, sepsis syndrome is the diagnosis. Septic shock ensues when systolic blood pressure (BP) decreases to less than the fifth percentile for age. If a patient in septic shock responds promptly to parenteral fluid administration and pharmacologic treatment, he or she is diagnosed with early septic shock. Shock that lasts for more than 1 hour despite vigorous therapeutic measures and necessitates vasopressor support is refractory septic shock. Finally, the presence of impaired organ perfusion accompanied by any combination of derangements, such as disseminated intravascular coagulation; acute respiratory distress syndrome (ARDS); and acute renal, hepatic, or neurologic dysfunction, is called multiple organ dysfunction syndrome (MODS).

The natural history of SIRS in adults has been evaluated in a multicenter, prospective study of 3708 patients with infection admitted to an ICU. A total of 69% of patients developed SIRS (7% of these patients died); 20% developed sepsis (16% of these patients died); 18% developed severe sepsis (20% of these patients died); and 4% developed septic shock (46% of these patients died). A similar prospective study of 1058 children admitted to a pediatric ICU (PICU)<sup>122 Redl-Wenzl E.M., Armbruster C., Edelmann G. , e al. The effects of norepinephrine on hemodynamics and renal function in severe septic shock states Intensive Care Med 1993 ;  19 : 151-154  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> showed that 82% developed SIRS, 23% developed sepsis, 4% developed severe sepsis, and 2% developed septic shock and that the overall mortality rate was 6%. In a different study, Naqvi<sup>108 Naqvi J.H., Chundu K.R., Friedman A.D. Shock in children with gram negative bacillary sepsis Haemophilus influenzae type B sepsis Pediatr Infect Dis 1986 ;  5 : 512-515  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> showed that the sepsis syndrome occurs in less than 25% of children with documented bacteremia and that blood cultures are negative in 40% of children with sepsis. The development of shock over time markedly increases the risk for death. Among patients with sepsis in whom shock does not develop, the mortality rate is 13%; among patients in whom shock is present on hospital admission, the mortality rate is 27%; among patients in whom shock develops in the first 24 hours, the mortality rate is 43%.<sup>17 Bone R.C., Fisher C.J., Clemmer T.P. , e al. Sepsis syndrome: A valid clinical entity. Methylprednisolone Severe Sepsis Study Group Crit Care Med 1989 ;  17 : 389-393  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup>

Septic shock develops in various clinical settings and is host or treatment related. Septic shock occurs in children with impaired immunity, such as neonates, or children with congenital immunodeficiencies, leukemia, cancer, or after chemotherapy. Children with congenital urinary tract abnormalities, congenital heart disease, extensive burns, or multiple trauma injuries and critically ill children with a prolonged stay in the ICU are also at increased risk. In adults and adolescents, translocation of bacteria from the gastrointestinal tract can complicate virtually any critical illness and lead to septic shock; this is less common in infants. In adults, sepsis is usually nosocomial or related to chronic disease with site-specific infections, such as abdominal sepsis, pneumonia, urinary tract infections, or infected intravascular devices. Many children with septic shock were previously healthy but develop septic shock that can be rapidly fatal. Infection with polysaccharide-escapulated organisms, such as meningococci, pneumococci, and Haemophilus influenzae, commonly is complicated by septic shock. Children less than 2 years of age who cannot make T-cell–independent antibody that is necessary to lyse polysaccharide-escapulated organisms have a predilection for infection with the earlier-mentioned organisms. The pathogens responsible for initiating septic shock in children vary with age and immunocompetence. In neonates, the primary organisms are group B β-hemolytic streptococci, Enterobacteriaceae, Listeria monocytogenes, Staphylococcus aureus, and Neisseria meningitis. In infants, the primary organisms are H. influenzae, Staphylococcus pneumoniae, S. aureus, and N. meningitis. In children, the primary organisms are S. pneumoniae, N. meningitis, S. aureus, and Enterobacteriaceae, and in immunocompromised children, the primary organisms are Enterobacteriaceae, S. aureus, Pseudomonadaceae, and Candida albicans.

It is important to diagnose the type of infection present so that rapid appropriate antibiotic therapy can be begun. Bryan<sup>23 Bryan C.S., Reynolds K.L., Brenner E.R. Analysis of 1,186 episodes of gram-negative bacteremi in non-university hospitals: The effects of antimicrobial therapy Rev Infect Dis 1983 ;  5 : 629-638  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> found that, in cases in which antibiotic therapy was appropriate, 72% of 2067 patients survived compared with only 55% of 538 patients surviving after initially inappropriate therapy. The type of organism causing the infection affects prognosis. Glauser et al<sup>56 Glauser M.P., Zanetti G., Baumgartner J.D. , e al. Septic shock: Pathogenesis Lancet 1991 ;  9 : 1220-1222

Cliccare qui per andare alla sezione Riferimenti</sup> found that 57% of 257 patients with gram-negative sepsis lived, 52% of 93 patients with gram-positive sepsis lived, 17% of 9 patients with fungal sepsis lived, and 73% of 212 patients with no growth on cultures lived.

In cases in which the antibiotics given to the patient lysed the isolated microorganisms, patient prognosis was improved significantly<sup>39 Craig W.A. Qualitative susceptibility tests versus quantitative MIC tests Diagn Microbiol Infect Dis 1993 ;  16 : 231-236  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup>; however, the desire to lyse the organism quickly with large doses of antibiotics should be tempered<sup>70 Hopkins R.A., Bull C., Haworth S.G. , e al. Pulmonary hypertensive crises following surgery for congenital heart defects in young children Eur J Cardiothorac Surg 1991 ;  5 : 628-634  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> with the knowledge that 4 to 6 hours after antibiotics have been given, systemic vasodilation and hypotension may occur. This occurrence is believed to be caused by the release of large amounts of toxin as a result of the antibiotics lysing large numbers of bacteria.<sup>72 Jaber B.L., Pereira B.J.G. Extracorporeal adsorbent-based strategies in sepsis Am J Kidney Dis 1997 ;  30 (suppl) : 44-56

Cliccare qui per andare alla sezione Riferimenti, 134 Singer M. Cardiac output in 1998 [review] Heart 1998 ;  79 : 425-428

Cliccare qui per andare alla sezione Riferimenti</sup> This condition can occur in gram-positive and gram-negative infection, and the systemic inflammatory response can be attenuated (and the shock decreased) in animals pretreated with steroids or nonsteroidal anti-inflammatory drugs.<sup>68 Hoffman J.N., Hartl W.H., Deppisch R. , e al. Effect of hemofiltration of hemodynamics and systemic concentrations of anaphylatoxins and cytokines in human sepsis Intensive Care Med 1996 ;  22 : 1360-1367

Cliccare qui per andare alla sezione Riferimenti, 75 Jenkins J.K., Carey P.D., Byrne K. , e al. Sepsis-inducted lung injury and effects of ibuprofen pretreatment: Analysis of early alveolar events via repetitive bronchoalveolar lavage Am Rev Respir Dis 1991 ;  143 : 155-161

Cliccare qui per andare alla sezione Riferimenti, 76 John S., Griesbach D., Baumgartel M. , e al. CVVH does not improve splanchnic microcirculation in septic shock compared to hemodialysis Intensive Care Med 1998 ;  24 (suppl) : 75

Cliccare qui per andare alla sezione Riferimenti</sup> A randomized trial of dexamethasone (0.2 mg/kg) given before antibiotic treatment in 72 children with sepsis<sup>136 Smith-Wright D.L., Green T.P., Lock J.E. , e al. Complications of vascular catheterization in critically ill children Crit Care Med 1984 ;  12 : 1015-1017  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> showed no benefit, however. Despite this study, the author still favors a single, small dose of hydrocortisone (25–50 mg) before and up to 1 hour after initiation of antibiotic therapy in patients with shock or who are likely to develop shock.