Nitric oxide provides myocardial protection when added to the cardiopulmonary bypass circuit during cardiac surgery: Randomized trial

Objectives: Cardiac surgery using cardiopulmonary bypass frequently provokes a systemic inflammatory response syndrome. This can lead to the development of low cardiac output syndrome (LCOS). Both of these can affect morbidity and mortality. This study is a systematic review of the impact of gaseous nitric oxide (gNO), delivered via the cardiopulmonary bypass (CPB) circuit during cardiac surgery, on post-operative outcomes. It aims to summarise the evidence available, to assess the effectiveness of gNO via the CPB circuit on outcomes, and highlight areas of further research needed to develop this hypothesis. Methods: A comprehensive search of Pubmed, Embase, Web of Science and the Cochrane Library was performed in May 2020. Only randomised control trials (RCTs) were considered. Results: Three studies were identified with a total of 274 patients. There was variation in the outcomes measures used across the studies. These studies demonstrate there is evidence that this intervention may contribute towards cardioprotection. Significant reductions in cardiac troponin I (cTnI) levels and lower vasoactive inotrope scores were seen in intervention groups. A high degree of heterogeneity between the studies exists. Meta-analysis of the duration of mechanical ventilation, length of ICU stay and length of hospital stay showed no significant differences. Conclusion: This systematic review explored the findings of three pilot RCTs. Overall the hypothesis that NO delivered via the CPB circuit can provide cardioprotection has been supported by this study. There remains a significant gap in the evidence, further high-quality research is required in both the adult and paediatric populations.

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Myocardial protection following del Nido cardioplegia in pediatric cardiac surgery

Asian Cardiovascular and Thoracic Annals ◽

10.1177/0218492318773589 ◽

2018 ◽

Vol 26 (4) ◽

pp. 267-272 ◽

Cited By ~ 3

Author(s):

Debasish Panigrahi ◽

Saibal Roychowdhury ◽

Rahul Guhabiswas ◽

Emmanuel Rupert ◽

Mrinalendu Das ◽

...

Keyword(s):

Intensive Care Unit ◽

Creatine Kinase ◽

Cardiac Surgery ◽

Intensive Care ◽

Cardiopulmonary Bypass ◽

Myocardial Protection ◽

Troponin I ◽

Blood Cardioplegia ◽

Cardioplegia Solution ◽

Creatine Kinase Mb

Background This study was designed to compare myocardial protection with del Nido cardioplegia and conventional blood cardioplegia in children undergoing cardiac surgery in Risk Adjustment for Congenital Heart Surgery categories 1 and 2. Methods Sixty patients were randomized into 2 groups receiving del Nido cardioplegia solution or conventional blood cardioplegia. Myocardial injury was assessed using biochemical markers (troponin I and creatine kinase-MB). Vasoactive-inotropic scores were calculated to compare inotropic requirements. Results Demographic characteristics, cardiopulmonary bypass time, and aortic crossclamp time were comparable in the 2 groups. Time-related changes in troponin I and creatine kinase-MB were similar in both groups. Statistically significant differences were seen in total cardioplegia volume requirement ( p < 0.0001), number of cardioplegia doses given ( p < 0.0001), packed red cell volume usage during cardiopulmonary bypass ( p < 0.02), and time taken to restore spontaneous regular rhythm ( p < 0.0001). Vasoactive-inotropic scores on transfer to the intensive care unit ( p < 0.040) and at 24 h ( p < 0.030) were significantly lower in the del Nido group. Duration of mechanical ventilation, intensive care unit stay, and hospital stay were comparable in the 2 groups. Conclusions Our results show that del Nido cardioplegia solution is as safe as conventional blood cardioplegia. Moreover, it provides the benefits of reduced dose requirement, lower consumption of allogenic blood on cardiopulmonary bypass, quicker resumption of spontaneous regular cardiac rhythm, and less inotropic support requirement on transfer to the intensive care unit and at 24 h, compared to conventional blood cardioplegia.

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Nitric oxide delivery during cardiopulmonary bypass reduces postoperative morbidity in children—a randomized trial

Journal of Thoracic and Cardiovascular Surgery ◽

10.1016/j.jtcvs.2012.09.100 ◽

2013 ◽

Vol 146 (3) ◽

pp. 530-536 ◽

Cited By ~ 43

Author(s):

Paul A. Checchia ◽

Ronald A. Bronicki ◽

Jared T. Muenzer ◽

David Dixon ◽

Steve Raithel ◽

...

Keyword(s):

Nitric Oxide ◽

Cardiopulmonary Bypass ◽

Randomized Trial ◽

Postoperative Morbidity ◽

Nitric Oxide Delivery

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Del Nido Cardioplegia Versus Cold Blood Cardioplegia in Adult Cardiac Surgery: Protocol for a Randomized Controlled Trial

JMIR Research Protocols ◽

10.2196/17826 ◽

2020 ◽

Vol 9 (7) ◽

pp. e17826

Author(s):

Jessica Garcia-Suarez ◽

Javier Garcia Fernandez ◽

Sergio Sanz ◽

Daniel Martinez Lopez ◽

Leticia Reques ◽

...

Keyword(s):

Clinical Trial ◽

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Myocardial Protection ◽

Primary Outcome ◽

Retrospective Studies ◽

Adult Patients ◽

Blood Cardioplegia ◽

Cardioplegia Solution ◽

Adult Cardiac Surgery

Background The use of cardioplegia solutions as a myocardial protection technique is essential during cardiac surgery with cardiopulmonary bypass. The del Nido cardioplegia solution (DNS) has been widely used as a myocardial preservation technique for pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Its unique pharmacological features have created growing interest for adult cardiac surgery, especially for elderly patients or those with ventricular dysfunction who are more prone to ischemia-reperfusion injury. Ever since its implementation, several retrospective studies have been published to validate the efficacy, safety, and efficiency of DNS in adult patients undergoing coronary revascularization, valve replacement, or combined procedures. Recently, a meta-analysis based on nine retrospective studies was published claiming the noninferiority of DNS compared to other conventional cardioplegia solutions. Few prospective randomized studies have been conducted whose primary outcome was the assessment of DNS clinical efficacy compared to other solutions commonly used in adult patients. Objective The aim of this randomized clinical trial is to assess the benefits of DNS compared to Cardi-Braun blood cardioplegia solution in clinical and biochemical terms regarding myocardial protection during adult cardiac surgery. Methods This is the protocol of a controlled, randomized, single-center clinical trial carried out at the Puerta de Hierro Majadahonda University Hospital in Spain. A total of 474 participants over the age of 18 years undergoing elective cardiac surgery with cardiopulmonary bypass will be assigned to groups by simple randomization to receive either DNS or Cardi-Braun blood cardioplegia solution. The primary outcome will be the differences between groups in myocardial protection in biochemical terms (ie, perioperative troponin levels) and clinical terms (ie, presence of the composite variable acute cardiovascular event). The clinical trial will be carried out under conditions of respect for the fundamental rights of the person and the ethical principles that affect biomedical research with human beings, as well as in accordance with international recommendations contained in the Declaration of Helsinki and its subsequent revisions. Results The inclusion process started in 2018. Data cleaning and analyses are expected to take place in the fall of 2020 and the results are expected in January 2021. Conclusions This study is particularly relevant as it will be one of the first to analyze the clinical effects of del Nido cardioplegia on the basis of direct myocardial protection parameters. In light of published studies, carrying out prospective studies based on primary clinical objectives with a larger sample, high-risk patients, and longer cardiopulmonary bypass times continues to be necessary. We believe that our study addresses an important gap in the knowledge of del Nido cardioplegia in adult patient cardiac surgery and will be able to clarify the possible benefits of this method in a large population of patients undergoing these procedures. Trial Registration European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2017-005144-14; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-005144-14+; ClinicalTrials.gov NCT04094168; https://clinicaltrials.gov/ct2/show/NCT04094168 International Registered Report Identifier (IRRID) DERR1-10.2196/17826

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P0323 / #365: EFFECTS OF INHALED NITRIC OXIDE ON HEMODYNAMICS AND GAS EXCHANGE IN CHILDREN AFTER HAVING UNDERGONE CARDIAC SURGERY UTILIZING CARDIOPULMONARY BYPASS

Pediatric Critical Care Medicine ◽

10.1097/01.pcc.0000739632.43669.17 ◽

2021 ◽

Vol 22 (Supplement 1 3S) ◽

pp. 175-175

Author(s):

E. Villarreal ◽

S. Flores ◽

R. Loomba ◽

S. Aiello

Keyword(s):

Nitric Oxide ◽

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Gas Exchange ◽

Inhaled Nitric Oxide

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A Study of Platelet Activation during Human Cardiopulmonary Bypass and the Effect of S-Nitrosoglutathione

Thrombosis and Haemostasis ◽

10.1055/s-0038-1665444 ◽

1997 ◽

Vol 78 (06) ◽

pp. 1516-1519 ◽

Cited By ~ 12

Author(s):

Edward J Langford ◽

Andrew Parfitt ◽

Adam J de Beider ◽

Michael T Marrinan ◽

John F Martin

Keyword(s):

Nitric Oxide ◽

Flow Cytometry ◽

Cardiac Surgery ◽

Cardiopulmonary Bypass ◽

Platelet Activation ◽

Surface Expression ◽

Platelet Inhibition ◽

Nitric Oxide Donor ◽

Platelet Dysfunction ◽

Platelet Surface

SummaryCardiac surgery is complicated by the occurrence of post-operative bleeding due to platelet dysfunction. This is largely caused by platelet activation and consumption during cardiopulmonary bypass. Patients undergoing cardiac surgery requiring cardiopulmonary bypass were studied to determine whether early platelet changes due to bypass could be inhibited using the platelet-selective nitric oxide donor S-nitroso-glutathione (GSNO). Flow cytometry was used to measure platelet surface expression of P-selectin (an α-granule protein) and glycoproteins (GP) IIb/IIIa and Ib (mediators of aggregation and adhesion) before and 5 and 10 min after commencing cardiopulmonary bypass, in 6 controls and 6 patients receiving GSNO 50 μg/min. Platelet P-selectin expression increased during bypass both in controls and patients receiving GSNO. Glycoproteins IIb/IIIa and Ib fell during bypass in control and GSNO-treated patients. There was no difference between control and GSNO-treated groups. Thus no significant platelet inhibition by S-nitrosoglutathione was demonstrated under these conditions.

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