Nitric Oxide During Cardiopulmonary Bypass in Neonates to Reduce Risk of Acute Kidney Injury

Children's Hospital Medical Center, Cincinnati

Overview

Acute kidney injury following cardiac surgery for congenital heart defects in children is a major cause of both short- and long-term morbidity and mortality, affecting up to 60% of high risk patients. Despite effort, to date, no successful therapeutic agent has gained widespread success in preventing this postoperative decline in renal function. Based on preliminary data available in the literature, we hypothesize that nitric oxide (gNO), administered during cardiopulmonary bypass (CPB), may reduce the risk of acute kidney injury (AKI) via mechanisms of reduced inflammation and vasodilation. In this pilot study, 40 neonates undergoing cardiac surgery will be randomized to receive intraoperative administration of 20 ppm of nitric oxide to the oxygenator of the cardiopulmonary bypass circuit or standard CPB with no additional gas.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Conditions

Acute Kidney Injury Congenital Heart Disease

Interventions

gases Nitric Oxide (gNO)DRUG

Participants in the intervention group will receive gNO blended into the fresh gas flow of the cardiopulmonary bypass (CPB) oxygenator and maintained at 20 ppm via an Ikaria INO Max DSIR (Mallinckrodt Pharmaceuticals, St. Louis, Missouri, USA), with continuous sampling of NO and NO2 concentration from a port adjacent to the oxygenator. The gNO delivery will be initiated when the patient is on CPB and stopped once the patient comes off CPB.

Eligibility

Sex: ALLMax age: 31 Days

Medical Language ↔ Plain English

Inclusion Criteria: * Neonates (≤31 days) undergoing cardiac surgery with cardiopulmonary bypass for congenital heart disease Exclusion Criteria: * 1\. Failure to obtain informed consent from parent/guardian, * Clinical signs of preoperative persistent elevated pulmonary vascular resistance, * Emergency surgery, * Episode of cardiac arrest within 1 week before surgery, * Recent treatment with steroids and/or a condition that may require treatment with steroids (excluding steroid administration specifically for CPB), * Use of inhaled NO (iNO) immediately prior to surgery, * Structural renal abnormalities by ultrasound, * Preoperative AKI, * Use of other investigational drugs, * Weight less than \<2.2 kg, * Gestational age \<36 weeks, * Major extracardiac congenital anomalies.

Outcomes

Primary Outcomes

Acute Kidney Injury

Occurrence of acute kidney defined by the Kidney Disease Improving Global Outcomes (KDIGO) diagnostic classification (employing both serum creatinine and urine output criteria).

Time frame: up to 72 hours postoperative

Glomerular Filtration Rate

Postoperative glomerular filtration rate (GFR) measured using serum cystatin C.

Time frame: up to 72 hours postoperative

Secondary Outcomes

Structural Kidney Injury

Assessed by measurement of urine biomarkers: neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18) liver-type fatty acid-binding protein (L-FABP), and urinary nitrate.

Time frame: up to 72 hours postoperative

Low cardiac output syndrome (LCOS)

Occurence of low cardiac output syndrome (LCOS) defined as any of the following at any time during the first 48 hours postoperative: 1. Lactate \>6mmol/l and central venous saturation (ScvO2) \<60% (or SaO2-ScvO2 difference greater than 35% in a single ventricle), 2. Vasoactive inotropic score (VIS)24 ≥ 10, 3. Extracorporeal Membrane Oxygenation (ECMO).

Time frame: up to 48 hours postoperative

Duration of mechanical ventilation

hours/days

Time frame: up to 2 weeks from admission to CICU to extubation

Length of cardiac intensive care unit (CICU) stay

days

Time frame: up to 2 weeksfrom admission to CICU to discharge from CICU

Length of hospital stay

Data from ClinicalTrials.gov

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