Dataset Information

Derangement of Arginine and Related Amino Acids in Children Undergoing Surgery for Congenital Heart Disease With Cardiopulmonary Bypass.

ABSTRACT: Arginine is a conditionally essential amino acid, the precursor for nitric oxide and a key factor in cell proliferation, protein synthesis, and energy metabolism. When there is increased demand in the setting of inflammation, ischemia-reperfusion injury, and organ dysfunction, endogenous arginine production falls short, and external supplementation may be necessary. The goal of this study was to assess changes in concentrations of plasma arginine, citrulline, ornithine, glutamine, and plasma arginase in infants and children undergoing surgery for congenital heart disease with cardiopulmonary bypass.

Design

Prospective observational study.

Setting

The study was conducted in the Heart Center at Texas Children's Hospital.

Subjects

Children undergoing surgery for congenital heart disease with cardiopulmonary bypass.

Interventions

None.

Measurements and main results

Serial perioperative blood samples were collected for quantification of amino acids, arginase, nitric oxide metabolites, and markers of organ function (lactate, Pao₂/Fio₂ ratio, and creatinine clearance). Thirty children (18 males) were included in the study; median (interquartile range) age 0.5 years (0.3-0.9 yr). The mean ± sd for plasma amino acid concentrations before cardiopulmonary bypass: arginine 62 ± 20 µmol/L, citrulline 24 ± 6 µmol/L, ornithine 53 ± 32 µmol/L, and glutamine 591 ± 126 µmol/L. Arginine concentration was decreased within the first 24 hours (43 ± 15 µmol/L; p = 0.004), citrulline and glutamine concentrations decreased over the first 48 hours (11 ± 4 µmol/L; p < 0.001 and 493 ± 131 µmol/L; p = 0.019, respectively) and were associated with an increase in arginase (3.8 ± 3 µg/mL; p < 0.05). There was an increase in Vasoactive-Inotropic Score (5.9 ± 19 vs 0.5 ± 2; p < 0.001), decrease in creatinine clearance (76 ± 24 vs 93 ± 31; p = 0.002), and Pao₂/Fio₂ ratio (243 ± 138 vs 374 ± 200; p = 0.007) comparing to baseline.

Conclusions

A widely variable degree of arginine, citrulline, and glutamine depletion occurs in children after surgery for congenital heart disease. These findings were associated with increased arginase and coincide with some of the markers of organ perfusion.

SUBMITTER: Navaei AH

PROVIDER: S-EPMC7368881 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Publications

Derangement of Arginine and Related Amino Acids in Children Undergoing Surgery for Congenital Heart Disease With Cardiopulmonary Bypass.

Navaei Amir H AH Shekerdemian Lara S LS Mohammad Mahmoud A MA Coss-Bu Jorge A JA Bastero Patricia P Ettinger Nicholas A NA Orellana Renan R Fernandes Caraciolo J CJ Marini Juan C JC

Critical care explorations 20200716 7

Arginine is a conditionally essential amino acid, the precursor for nitric oxide and a key factor in cell proliferation, protein synthesis, and energy metabolism. When there is increased demand in the setting of inflammation, ischemia-reperfusion injury, and organ dysfunction, endogenous arginine production falls short, and external supplementation may be necessary. The goal of this study was to assess changes in concentrations of plasma arginine, citrulline, ornithine, glutamine, and plasma arg ...[more]

PMID: 32766551

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Project description:ObjectivesTo 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).DesignProspective observational study.SettingTwelve-bed cardiac ICU in a university-affiliated children's hospital.PatientsChildren 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 resultsPlasma 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.ConclusionsIn 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.

Project description:ImportanceIn children undergoing heart surgery, nitric oxide administered into the gas flow of the cardiopulmonary bypass oxygenator may reduce postoperative low cardiac output syndrome, leading to improved recovery and shorter duration of respiratory support. It remains uncertain whether nitric oxide administered into the cardiopulmonary bypass oxygenator improves ventilator-free days (days alive and free from mechanical ventilation).ObjectiveTo determine the effect of nitric oxide applied into the cardiopulmonary bypass oxygenator vs standard care on ventilator-free days in children undergoing surgery for congenital heart disease.Design, setting, and participantsDouble-blind, multicenter, randomized clinical trial in 6 pediatric cardiac surgical centers in Australia, New Zealand, and the Netherlands. A total of 1371 children younger than 2 years undergoing congenital heart surgery were randomized between July 2017 and April 2021, with 28-day follow-up of the last participant completed on May 24, 2021.InterventionsPatients were assigned to receive nitric oxide at 20 ppm delivered into the cardiopulmonary bypass oxygenator (n = 679) or standard care cardiopulmonary bypass without nitric oxide (n = 685).Main outcomes and measuresThe primary end point was the number of ventilator-free days from commencement of bypass until day 28. There were 4 secondary end points including a composite of low cardiac output syndrome, extracorporeal life support, or death; length of stay in the intensive care unit; length of stay in the hospital; and postoperative troponin levels.ResultsAmong 1371 patients who were randomized (mean [SD] age, 21.2 [23.5] weeks; 587 girls [42.8%]), 1364 (99.5%) completed the trial. The number of ventilator-free days did not differ significantly between the nitric oxide and standard care groups, with a median of 26.6 days (IQR, 24.4 to 27.4) vs 26.4 days (IQR, 24.0 to 27.2), respectively, for an absolute difference of -0.01 days (95% CI, -0.25 to 0.22; P = .92). A total of 22.5% of the nitric oxide group and 20.9% of the standard care group developed low cardiac output syndrome within 48 hours, needed extracorporeal support within 48 hours, or died by day 28, for an adjusted odds ratio of 1.12 (95% CI, 0.85 to 1.47). Other secondary outcomes were not significantly different between the groups.Conclusions and relevanceIn children younger than 2 years undergoing cardiopulmonary bypass surgery for congenital heart disease, the use of nitric oxide via cardiopulmonary bypass did not significantly affect the number of ventilator-free days. These findings do not support the use of nitric oxide delivered into the cardiopulmonary bypass oxygenator during heart surgery.Trial registrationanzctr.org.au Identifier: ACTRN12617000821392.

Dataset Information

Derangement of Arginine and Related Amino Acids in Children Undergoing Surgery for Congenital Heart Disease With Cardiopulmonary Bypass.

Design

Setting

Subjects

Interventions

Measurements and main results

Conclusions

Publications

Derangement of Arginine and Related Amino Acids in Children Undergoing Surgery for Congenital Heart Disease With Cardiopulmonary Bypass.

Similar Datasets

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