Table 1 |
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Immunomodulating agents in neonatal and adult sepsis |
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Agent |
Neonates |
Adults |
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Steroids |
No evidence of improved outcome in critically ill infants or children with sepsis [89] |
High-dose: no benefit [101] or reduction in mortality [102], may actually increase mortality [86] |
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Hemodynamically stable: no benefit [101] |
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Low-dose, long-course: may decrease mortality [87] |
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Intravenous immunoglobulin |
Prevention: 3% reduction in sepsis, 4% reduction in any serious infection; no change in mortality, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage or length of stay [103] |
Polyclonal: significant reduction in mortality [105] |
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Suspected infection: decrease in mortality of borderline statistical significance [104] |
Monoclonal: HA-1A, E5, IL-1, phospholipase A2, adhesion molecules and contact factors all show no benefit [86] |
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Proven infection: no change in mortality [104] |
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Colony-stimulating factors |
Treatment: rhG-CSF and rhGM-CSF not effective in reducing mortality [106,107] |
rhG-CSF in pneumonia with severe sepsis: no difference in mortality, ARDS or adverse events [108,109]; no difference in days of ventilatory support or intensive care unit stay [108] |
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Prophylaxis: both agents effective in correcting neutropenia in premature neonates [106 107]; rhGM-CSF may decrease infection in infants <32 weeks who are neutropenic or at risk for developing neutropenia [106,107]; rhGM-CSF decreases mortality in neutropenic neonates with sepsis [107] |
rhG-CSF in severe sepsis: small study shows a significant decrease in mortality [110] |
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rhG-CSF febrile neutropenia: shorter hospital stay, no difference in mortality [111] |
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rhGM-CSF in severe sepsis: no change in mortality [112,113]; improved PaO2/FiO2 ratio [112] and clearance of infection [113] |
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Activated protein C |
No randomized trials in neonates [114,115] |
Severe sepsis and increased risk of death: improved organ function and decreased mortality [114]; 19.4% reduction in relative risk of death [84]; cost-effective [117] |
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Two case reports with survival without adverse events [114,116] |
Severe sepsis and low risk of death: no benefit [118] |
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Large pediatric clinical trial stopped early due to no improvement in mortality and increased intracranial hemorrhage [98] |
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Pentoxifylline |
Decreased mortality, circulatory compromise, disseminated intravascular coagulopathy and necrotizing enterocolitis versus placebo [94] |
Improved cardiopulmonary function [96] and hemodynamic performance [95] |
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Reduces mortality without adverse effects [119] |
No change in 28-day mortality [95] |
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No adverse effects [95,96] |
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ARDS, acute respiratory distress syndrome; rhG-CSF, recombinant human granulocyte colony-stimulating factor; rhGM-CSF, recombinant human granulocyte–macrophage colony-stimulating factor. |
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Luce et al. Critical Care 2007 11:228 doi:10.1186/cc6091 |
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