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Early postoperative monocyte deactivation predicts systemic inflammation and prolonged stay in pediatric cardiac
Meredith L Allen1, Mark J Peters, Allan Goldman
1Immunobiology Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK. m.allen@ich.ucl.ac.uk
Insights
Low monocyte human lymphocyte antigen (HLA)-DR expression after cardiopulmonary bypass in children indicates a high risk for developing sepsis or systemic inflammatory response syndrome (SIRS). Monitoring HLA-DR may help identify at-risk pediatric patients. Keywords: sepsis, SIRS, cardiopulmonary bypass, HLA-DR, pediatric cardiac surgery.
Area of Science:
- Pediatric critical care medicine
- Immunology
- Cardiovascular surgery
Background:
- Sepsis and systemic inflammatory response syndrome (SIRS) are significant causes of mortality in pediatric patients undergoing cardiopulmonary bypass (CPB).
- Previous strategies targeting pro-inflammatory mediators have not improved outcomes.
- Monocyte human lymphocyte antigen (HLA)-DR expression may reflect the balance between pro- and anti-inflammatory responses, with low levels suggesting immunodeficiency.
Purpose of the Study:
- To investigate the association between monocyte HLA-DR expression and the development of sepsis/SIRS in children after CPB.
- To determine if low HLA-DR expression is an independent predictor of sepsis/SIRS in this population.
Main Methods:
- Prospective, observational clinical study conducted at a tertiary pediatric cardiac center.
- Eighty-two pediatric patients undergoing elective cardiac surgery with CPB were enrolled.
- Monocyte HLA-DR expression was measured before and after surgery.
Main Results:
- CPB significantly decreased monocyte HLA-DR expression in all children, with the lowest levels observed within 72 hours post-surgery.
- Significantly lower HLA-DR concentrations were found in patients requiring prolonged intensive care.
- Monocyte HLA-DR expression below 60% was associated with a 12.9-fold increased risk of developing sepsis/SIRS (p <.0001).
- Low HLA-DR independently predicted sepsis/SIRS development, even after adjusting for clinical factors.
Conclusions:
- Decreased early postoperative monocyte HLA-DR expression identifies pediatric patients at substantially increased risk for subsequent sepsis/SIRS.
- These findings suggest that monitoring HLA-DR levels could aid in identifying high-risk subpopulations.
- Interventions aimed at mitigating this risk in patients with low HLA-DR warrant further investigation.
Objective:
Sepsis and systemic inflammatory response syndrome (SIRS) are major causes of morbidity and mortality after cardiopulmonary bypass. Attempts to suppress proinflammatory mediators have failed to improve outcomes in sepsis or in patients undergoing cardiopulmonary bypass. Recent work in adult patients has suggested that the balance between pro- and anti-inflammatory mediators is more important than the level of proinflammatory response alone. This balance may be reflected by the expression of monocyte human lymphocyte antigen (HLA)-DR, with low concentrations indicating an excess of anti-inflammatory stimuli and relative immunodeficiency. We investigated the relationship between monocyte HLA-DR expression and the subsequent development of sepsis/SIRS in children undergoing cardiopulmonary bypass.
Design:
A prospective, observational, clinical study.
Setting:
A tertiary pediatric cardiac center.
Patients:
Eighty-two infants and children undergoing elective cardiac surgery between March and December 1999.
Measurements And Main Results:
Monocyte HLA-DR expression was assessed before and after surgery and was found to be related to the length of hospital stay and the development of complications including sepsis/SIRS. The inflammatory insult of cardiopulmonary bypass decreased monocyte HLA-DR expression in all children. Lowest concentrations were seen within 72 hrs of surgery and were significantly lower in cases that subsequently required prolonged intensive care support (p <.0001, Mann-Whitney). HLA-DR expression on <60% of circulating monocytes was associated with a greatly increased risk of later (minimum 4 days) development of sepsis/SIRS (odds ratio, 12.9; 95% confidence interval, 3.4-47.5). Low HLA-DR was an independent predictor for the development of sepsis/SIRS after correction for age, bypass time, complexity of surgery, Paediatric Index of Mortality, and surgeon on multiple logistic regression analysis.
Conclusions:
Patients with decreased HLA-DR in the early postoperative period represent a subpopulation at greatly increased risk of later sepsis/SIRS. Such patients may benefit from strategies aimed to reduce this risk.