A randomized and blinded trial of inhaled nitric oxide in a piglet model of pediatric cardiopulmonary resuscitation

Ryan W Morgan; Robert M Sutton; Adam S Himebauch; Anna L Roberts; William P Landis; Yuxi Lin; Jonathan Starr; Abhay Ranganathan; Nile Delso; Constantine D Mavroudis; Lindsay Volk; Julia Slovis; Alexandra M Marquez; Vinay M Nadkarni; Marco Hefti; Robert A Berg; Todd J Kilbaugh

doi:10.1016/j.resuscitation.2021.03.004

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A randomized and blinded trial of inhaled nitric oxide in a piglet model of pediatric cardiopulmonary resuscitation

Journal article

Peer reviewed

A randomized and blinded trial of inhaled nitric oxide in a piglet model of pediatric cardiopulmonary resuscitation

Ryan W Morgan, Robert M Sutton, Adam S Himebauch, Anna L Roberts, William P Landis, Yuxi Lin, Jonathan Starr, Abhay Ranganathan, Nile Delso, Constantine D Mavroudis, …

Resuscitation, Vol.162, pp.274-283

05/2021

DOI: 10.1016/j.resuscitation.2021.03.004

PMID: 33766668

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Abstract

Inhaled nitric oxide (iNO) during cardiopulmonary resuscitation (CPR) improved systemic hemodynamics and outcomes in a preclinical model of adult in-hospital cardiac arrest (IHCA) and may also have a neuroprotective role following cardiac arrest. The primary objectives of this study were to determine if iNO during CPR would improve cerebral hemodynamics and mitochondrial function in a pediatric model of lipopolysaccharide-induced shock-associated IHCA. After lipopolysaccharide infusion and ventricular fibrillation induction, 20 1-month-old piglets received hemodynamic-directed CPR and were randomized to blinded treatment with or without iNO (80 ppm) during and after CPR. Defibrillation attempts began at 10 min with a 20-min maximum CPR duration. Cerebral tissue from animals surviving 1-h post-arrest underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and immunohistochemical analyses to assess neuropathology. During CPR, the iNO group had higher mean aortic pressure (41.6 ± 2.0 vs. 36.0 ± 1.4 mmHg; p = 0.005); diastolic BP (32.4 ± 2.4 vs. 27.1 ± 1.7 mmHg; p = 0.03); cerebral perfusion pressure (25.0 ± 2.6 vs. 19.1 ± 1.8 mmHg; p = 0.02); and cerebral blood flow relative to baseline (rCBF: 243.2 ± 54.1 vs. 115.5 ± 37.2%; p = 0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O2/s mg; p = 0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O2/s mg; p = 0.02). There were no other differences in mitochondrial respiration or brain injury between groups. Treatment with iNO during CPR resulted in superior systemic hemodynamics, rCBF, and cerebral mitochondrial Complex I respiration in this pediatric cardiac arrest model.

Shock

Pediatrics

In-hospital cardiac arrest

Cerebral blood flow

Cardiopulmonary resuscitation

Inhaled nitric oxide

Physiology

Hemodynamics

Laboratory

Pulmonary hypertension

Details

Title: Subtitle: A randomized and blinded trial of inhaled nitric oxide in a piglet model of pediatric cardiopulmonary resuscitation
Creators: Ryan W Morgan - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Robert M Sutton - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Adam S Himebauch - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Anna L Roberts - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
William P Landis - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Yuxi Lin - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Jonathan Starr - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Abhay Ranganathan - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Nile Delso - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Constantine D Mavroudis - Department of Surgery, Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, United States
Lindsay Volk - Department of Surgery, Division of Cardiothoracic Surgery, Children’s Hospital of Philadelphia, United States
Julia Slovis - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Alexandra M Marquez - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Vinay M Nadkarni - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Marco Hefti - Department of Pathology, University of Iowa Carver College of Medicine, United States
Robert A Berg - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Todd J Kilbaugh - Department of Anesthesiology and Critical Care Medicine, Children’s Hospital of Philadelphia, United States
Resource Type: Journal article
Publication Details: Resuscitation, Vol.162, pp.274-283
DOI: 10.1016/j.resuscitation.2021.03.004
PMID: 33766668
NLM abbreviation: Resuscitation
ISSN: 0300-9572
eISSN: 1873-1570
Publisher: Elsevier B.V
Grant note: DOI: 10.13039/100000002, name: National Institutes of Health
Language: English
Date published: 05/2021
Academic Unit: Pathology; Iowa Neuroscience Institute
Record Identifier: 9984070565202771

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