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Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass
Stephan Christen1, Barbara Finckh, Jens Lykkesfeldt
1Institute for Infectious Diseases, University of Berne, Friedbuehlstrasse 51, CH-3010 Berne, Switzerland. stephan.christen@ifik.unibe.ch
Insights
Pediatric patients undergoing cardiopulmonary bypass (CPB) experience significant oxidative stress, primarily due to hemolysis, leading to postoperative complications. Minimizing hemolysis or using antioxidant treatments may reduce these risks.
Area of Science:
- Cardiovascular Surgery
- Pediatric Cardiology
- Biochemistry
Background:
- Cardiopulmonary bypass (CPB) is associated with postoperative complications in pediatric patients.
- Oxidative stress is a suspected contributor to these complications.
- Pediatric patients may be more vulnerable to CPB-related oxidative stress.
Purpose of the Study:
- To measure oxidative stress markers in children undergoing heart surgery with CPB.
- To investigate the relationship between oxidative stress, inflammation, and iron status post-CPB.
- To identify the primary cause of early oxidative stress in pediatric CPB.
Main Methods:
- Blood plasma samples collected from 20 children before, during, and up to 48 hours after CPB.
- Measurement of oxidative stress markers (ascorbate, dehydroascorbate, malondialdehyde).
- Assessment of inflammatory parameters (IL-6, IL-8) and iron status.
Main Results:
- Ascorbate levels decreased by 50% during CPB, correlating with increased dehydroascorbate and malondialdehyde.
- Peak inflammatory markers (IL-6, IL-8) occurred 3-12 hours post-CPB.
- Early oxidative stress correlated with CPB duration, plasma hemoglobin, and IL-6/IL-8, suggesting hemolysis as the main cause.
Conclusions:
- Hemolysis, not inflammation or ischemia, is the primary driver of early oxidative stress in pediatric CPB.
- Hemolysis-induced oxidative stress may contribute to pulmonary dysfunction after CPB.
- Strategies to minimize hemolysis or oxidative stress are crucial for reducing pediatric CPB complications.
Abstract:
Oxidative stress seems to contribute to cardiopulmonary bypass (CPB)-related postoperative complications. Pediatric patients are particularly prone to these complications. With this in mind, we measured oxidative stress markers in blood plasma of 20 children undergoing elective heart surgery before, during, and up to 48 h after cessation of CPB, along with inflammatory parameters and full analysis of iron status. Ascorbate levels were decreased by approximately 50% (P < 0.001) at the time of aorta cross-clamp removal (or pump switch-off in 4 patients with partial CPB), and associated with corresponding increases in dehydroascorbate (P < 0.001, r = -0.80) and malondialdehyde (P < 0.01, r = -0.59). In contrast to the immediate oxidative response, peak levels of IL-6 and IL-8 were not observed until 3-12 h after CPB cessation. The early loss of ascorbate correlated with duration of CPB (P < 0.002, r = 0.72), plasma hemoglobin after cross-clamp removal (P < 0.001, r = 0.70), and IL-6 and IL-8 levels at 24 and 48 h after CPB (P < 0.01), but not with postoperative lactate levels, strongly suggesting that hemolysis, and not inflammation or ischemia, was the main cause of early oxidative stress. The correlation of ventilation time with early changes in ascorbate (P < 0.02, r = 0.55), plasma hemoglobin (P < 0.01, r = 0.60), and malondialdehyde (P < 0.02, r = 0.54) suggests that hemolysis-induced oxidative stress may be an underlying cause of CPB-associated pulmonary dysfunction. Optimization of surgical procedures or therapeutic intervention that minimize hemolysis (e.g., off-pump surgery) or the resultant oxidative stress (e.g., antioxidant treatment) should be considered as possible strategies to lower the rate of postoperative complications in pediatric CPB.
