title: Inflammatory reaction and capillary leak syndrome related to cardiopulmonary bypass in neonates undergoing cardiac operations.
abstract: We studied the inflammatory reaction related to cardiopulmonary bypass in 24 neonates (median age 6 days) undergoing the arterial switch operation for simple transposition of the great arteries, with respect to the development of postoperative capillary leak syndrome. Complement proteins, leukocyte count, tumor necrosis factor-alpha, and histamine levels were determined before, during, and after cardiopulmonary bypass. Additionally, protein movement from the intravascular into the extravascular space during cardiopulmonary bypass was assessed by the measurement of plasma concentrations of proteins with molecular weights ranging from 21,200 to 718,000. Capillary leak syndrome developed in 13 of the 24 neonates. Patients with capillary leak syndrome, as compared with those without, had preoperatively higher C5a levels (C5a, 3.0 +/- 0.6 microgram/L vs 0.9 +/- 0.2 microgram/L) (mean +/- standard error of the mean) (p < 0.05) and higher leukocyte counts (leukocytes, 17.9 +/- 2.1 X 10(3) cells/ml versus 11.7 +/- 0.8 X 10(3) cells/ml) (p < 0.05), suggesting in these neonates a preoperative inflammatory state. Preoperative clinical and operative data were identical in both patient groups. Before cardiopulmonary bypass, serum protein concentrations were similar in all patients. Ten minutes after institution of cardiopulmonary bypass, protein concentrations fell to significantly lower values in patients with capillary leak syndrome than in those without: albumin (19% +/- 1.5% vs 30% +/- 6% of the prebypass value, p < 0.05), immunoglobulin G (17% +/- 1.5% vs 29% +/- 5.5%, p < 0.001), and alpha 2-macroglobulin (15% +/- 1.2% vs 25% +/- 4%, p < 0.02). During cardiopulmonary bypass, albumin concentrations remained significantly lower in patients with capillary leak syndrome than in those without, whereas hematocrit values were similar in both groups. During cardiopulmonary bypass, patients with capillary leak syndrome also had lower concentrations of complement proteins C3 and C4 but not C1 inhibitor. C3d/C3 ratio and C5a levels were similar in both patient groups. In contrast, histamine liberation during cardiopulmonary bypass was significantly more pronounced in patients with capillary leak syndrome than in those without (725.2 +/- 396.7 pg/ml vs -54.1 +/- 58.4 pg/ml, p < 0.05). Tumor necrosis factor-alpha levels after protamine administration were also significantly higher in patients with capillary leak syndrome (38.1 +/- 10.0 pg/ml vs 15.3 +/- 3.4 pg/ml, p < 0.05). Leukocyte count during and after cardiopulmonary bypass was similar in both patient groups. This study demonstrates increased protein leakage as early as 10 minutes after initiation of.
authors.affiliation: Department of Pediatric Cardiology, Aachen University of Technology, Germany.
authors.forename: M C
authors.initials: MC
authors.lastname: Seghaye
authors.forename: R G
authors.initials: RG
authors.lastname: Grabitz
authors.forename: J
authors.initials: J
authors.lastname: Duchateau
authors.forename: S
authors.initials: S
authors.lastname: Busse
authors.forename: S
authors.initials: S
authors.lastname: Däbritz
authors.forename: D
authors.initials: D
authors.lastname: Koch
authors.forename: G
authors.initials: G
authors.lastname: Alzen
authors.forename: H
authors.initials: H
authors.lastname: Hörnchen
authors.forename: B J
authors.initials: BJ
authors.lastname: Messmer
authors.forename: G
authors.initials: G
authors.lastname: Von Bernuth
mesh_terms: D000210:Acute-Phase Reaction / Q000209:etiology*; D001798:Blood Proteins / Q000032:analysis; D002199:Capillary Permeability; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003174:Complement C1 Inactivator Proteins / Q000032:analysis; D003176:Complement C3 / Q000032:analysis; D015933:Complement C3d / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D015936:Complement C5a / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis; D006400:Hematocrit; D006494:Heparin Antagonists / Q000008:administration & dosage; D006632:Histamine / Q000097:blood; D006636:Histamine Release; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007231:Infant, Newborn; D007958:Leukocyte Count; D008970:Molecular Weight; D011183:Postoperative Complications; D011479:Protamines / Q000008:administration & dosage; D012709:Serum Albumin / Q000032:analysis; D013577:Syndrome; D013997:Time Factors; D014188:Transposition of Great Vessels / Q000601:surgery*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D000511:alpha-Macroglobulins / Q000032:analysis
chemical_list: D001798:Blood Proteins; D003174:Complement C1 Inactivator Proteins; D003176:Complement C3; D003181:Complement C4; D006494:Heparin Antagonists; D007074:Immunoglobulin G; D011479:Protamines; D012709:Serum Albumin; D014409:Tumor Necrosis Factor-alpha; D000511:alpha-Macroglobulins; D015933:Complement C3d; D015936:Complement C5a; D006632:Histamine; D003165:Complement System Proteins