Immunoparalysis and nosocomial infection in children with multiple organ dysfunction syndrome.

Abstract

PURPOSE:

Immunoparalysis defined by prolonged monocyte human leukocyte antigen DR depression is associated with adverse outcomes in adult severe sepsis and can be reversed with granulocyte macrophage colony-stimulating factor (GM-CSF). We hypothesized that immunoparalysis defined by whole-blood ex vivo lipopolysaccharide-induced tumor necrosis factor-alpha (TNFα) response <200 pg/mL beyond day 3 of multiple organ dysfunction syndrome (MODS) is similarly associated with nosocomial infection in children and can be reversed with GM-CSF.

METHODS:

In study period 1, we performed a multicenter cohort trial of transplant and nontransplant multiple organ dysfunction syndrome (MODS) patients (≥2 organ failure). In study period 2, we performed an open-label randomized trial of GM-CSF therapy for nonneutropenic, nontransplant, severe MODS patients (≥3 organ failure) with TNFα response <160 pg/mL.

RESULTS:

Immunoparalysis was observed in 34% of MODS patients (n = 70) and was associated with increased nosocomial infection (relative risk [RR] 3.3, 95% confidence interval [1.8-6.0] p < 0.05) and mortality (RR 5.8 [2.1-16] p < 0.05). TNFα response <200 pg/mL throughout 7 days after positive culture was associated with persistent nosocomial infection, whereas recovery above 200 pg/mL was associated with resolution of infection (p < 0.05). In study period 2, GM-CSF therapy facilitated rapid recovery of TNFα response to >200 pg/mL by 7 days (p < 0.05) and prevented nosocomial infection (no infections in seven patients versus eight infections in seven patients) (p < 0.05).

CONCLUSIONS:

Similar to in adults, immunoparalysis is a potentially reversible risk factor for development of nosocomial infection in pediatric MODS. Whole-blood ex vivo TNFα response is a promising biomarker for monitoring this condition.

• Authors: Mark W Hall, Nina L Knatz, Carol Vetterly, Steven Tomarello, Mark D Wewers, Hans Dieter Volk, Joseph A Carcillo
• Journal: Intensive care medicine (Intensive Care Med) Vol. 37 Issue 3 Pg. 525-32 (Mar 2011) ISSN: 1432-1238 [Electronic] United States
• PMID: 21153402 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Tumor Necrosis Factor-alpha
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Adolescent
• Child
• Child, Preschool
• Cohort Studies
• Confidence Intervals
• Cross Infection (drug therapy, etiology, immunology)
• Granulocyte-Macrophage Colony-Stimulating Factor (therapeutic use)
• Humans
• Immunity, Innate (drug effects)
• Immunocompromised Host (drug effects)
• Infant
• Interleukin-6 (blood)
• Multiple Organ Failure (immunology, physiopathology)
• Severity of Illness Index
• Tumor Necrosis Factor-alpha (blood)
• United States