Bioactive Oxylipins in Infants and Children With Congenital Heart Disease Undergoing Pediatric Cardiopulmonary Bypass

Pediatr Crit Care Med. 2020 Jan;21(1):33-41. doi: 10.1097/PCC.0000000000002036.

Abstract

Objectives: To determine the production of 9-hydroxyoctadecadienoic acid and 13-hydroxyoctadecadienoic acid during cardiopulmonary bypass in infants and children undergoing cardiac surgery, evaluate their relationship with increase in cell-free plasma hemoglobin, provide evidence of bioactivity through markers of inflammation and vasoactivity (WBC count, milrinone use, vasoactive-inotropic score), and examine their association with overall clinical burden (ICU/hospital length of stay and mechanical ventilation duration).

Design: Prospective observational study.

Setting: Twelve-bed cardiac ICU in a university-affiliated children's hospital.

Patients: Children were prospectively enrolled during their preoperative clinic appointments with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass INTERVENTIONS:: None.

Measurements and main results: Plasma was collected at the start and end of cardiopulmonary bypass in 34 patients. 9-hydroxyoctadecadienoic acid, 13-hydroxyoctadecadienoic acid, plasma hemoglobin, and WBC increased. 9:13-hydroxyoctadecadienoic acid at the start of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours postcardiopulmonary bypass (R = 0.25; p < 0.01), milrinone use (R = 0.17; p < 0.05), and WBC (R = 0.12; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the end of cardiopulmonary bypass was associated with vasoactive-inotropic score at 2-24 hours (R = 0.17; p < 0.05), 24-48 hours postcardiopulmonary bypass (R = 0.12; p < 0.05), and milrinone use (R = 0.19; p < 0.05). 9:13-hydroxyoctadecadienoic acid at the start and end of cardiopulmonary bypass were associated with the changes in plasma hemoglobin (R = 0.21 and R = 0.23; p < 0.01). The changes in plasma hemoglobin was associated with milrinone use (R = 0.36; p < 0.001) and vasoactive-inotropic score less than 2 hours (R = 0.22; p < 0.01), 2-24 hours (R = 0.24; p < 0.01), and 24-48 hours (R = 0.48; p < 0.001) postcardiopulmonary bypass. Cardiopulmonary bypass duration, 9:13-hydroxyoctadecadienoic acid at start of cardiopulmonary bypass, and plasma hemoglobin may be risk factors for high vasoactive-inotropic score. Cardiopulmonary bypass duration, changes in plasma hemoglobin, 9:13-hydroxyoctadecadienoic acid, and vasoactive-inotropic score correlate with ICU and hospital length of stay and/mechanical ventilation days.

Conclusions: In low-risk pediatric patients undergoing cardiopulmonary bypass, 9:13-hydroxyoctadecadienoic acid was associated with changes in plasma hemoglobin, vasoactive-inotropic score, and WBC count, and may be a risk factor for high vasoactive-inotropic score, indicating possible inflammatory and vasoactive effects. Further studies are warranted to delineate the role of hydroxyoctadecadienoic acids and plasma hemoglobin in cardiopulmonary bypass-related dysfunction and to explore hydroxyoctadecadienoic acid production as a potential therapeutic target.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / blood
  • Cardiac Surgical Procedures / adverse effects
  • Cardiac Surgical Procedures / methods
  • Cardiopulmonary Bypass / adverse effects
  • Cardiopulmonary Bypass / methods*
  • Child
  • Child, Preschool
  • Fatty Acids, Unsaturated / blood*
  • Fatty Acids, Unsaturated / metabolism
  • Female
  • Heart Defects, Congenital / drug therapy
  • Heart Defects, Congenital / surgery*
  • Hemoglobins / analysis
  • Humans
  • Infant
  • Intensive Care Units
  • Length of Stay
  • Leukocyte Count
  • Linoleic Acids / blood*
  • Linoleic Acids / metabolism
  • Male
  • Milrinone / therapeutic use
  • Oxylipins / blood*
  • Oxylipins / metabolism
  • Prospective Studies
  • Respiration, Artificial
  • Risk Factors
  • Vasodilator Agents / therapeutic use

Substances

  • 9-hydroxyoctadecadienoic acid
  • Biomarkers
  • Fatty Acids, Unsaturated
  • Hemoglobins
  • Linoleic Acids
  • Oxylipins
  • Vasodilator Agents
  • 13-hydroxy-9,11-octadecadienoic acid
  • Milrinone