Table 1 Immunomodulating agents in neonatal and adult sepsis

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]

Hemodynamically stable: no benefit [101]

Low-dose, long-course: may decrease mortality [87]

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]

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]

Proven infection: no change in mortality [104]

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]

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]

rhG-CSF febrile neutropenia: shorter hospital stay, no difference in mortality [111]

rhGM-CSF in severe sepsis: no change in mortality [112,113]; improved PaO2/FiO₂ ratio [112] and clearance of infection [113]

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]

Two case reports with survival without adverse events [114,116]

Severe sepsis and low risk of death: no benefit [118]

Large pediatric clinical trial stopped early due to no improvement in mortality and increased intracranial hemorrhage [98]

Pentoxifylline

Decreased mortality, circulatory compromise, disseminated intravascular coagulopathy and necrotizing enterocolitis versus placebo [94]

Improved cardiopulmonary function [96] and hemodynamic performance [95]

Reduces mortality without adverse effects [119]

No change in 28-day mortality [95]

No adverse effects [95,96]