scholarly journals Study protocol: NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC trial): a randomised controlled trial

BMJ Open ◽  
2019 ◽  
Vol 9 (8) ◽  
pp. e026664 ◽  
Author(s):  
Luregn J Schlapbach ◽  
Stephen Brian Horton ◽  
Debbie Amanda Long ◽  
John Beca ◽  
Simon Erickson ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Standard Care ◽  
Congenital Heart ◽  
Heart Defects ◽  
Controlled Trial ◽  
Invasive Mechanical Ventilation ◽  
Double Blind ◽  
Low Cardiac Output Syndrome ◽  
The Impact

IntroductionCongenital heart disease (CHD) is a major cause of infant mortality. Many infants with CHD require corrective surgery with most operations requiring cardiopulmonary bypass (CPB). CPB triggers a systemic inflammatory response which is associated with low cardiac output syndrome (LCOS), postoperative morbidity and mortality. Delivery of nitric oxide (NO) into CPB circuits can provide myocardial protection and reduce bypass-induced inflammation, leading to less LCOS and improved recovery. We hypothesised that using NO during CPB increases ventilator-free days (VFD) (the number of days patients spend alive and free from invasive mechanical ventilation up until day 28) compared with standard care. Here, we describe the NITRIC trial protocol.Methods and analysisThe NITRIC trial is a randomised, double-blind, controlled, parallel-group, two-sided superiority trial to be conducted in six paediatric cardiac surgical centres. One thousand three-hundred and twenty infants <2 years of age undergoing cardiac surgery with CPB will be randomly assigned to NO at 20 ppm administered into the CPB oxygenator for the duration of CPB or standard care (no NO) in a 1:1 ratio with stratification by age (<6 and ≥6 weeks), single ventricle physiology (Y/N) and study centre. The primary outcome will be VFD to day 28. Secondary outcomes include a composite of LCOS, need for extracorporeal membrane oxygenation or death within 28 days of surgery; length of stay in intensive care and in hospital; and, healthcare costs. Analyses will be conducted on an intention-to-treat basis. Preplanned secondary analyses will investigate the impact of NO on host inflammatory profiles postsurgery.Ethics and disseminationThe study has ethical approval (HREC/17/QRCH/43, dated 26 April 2017), is registered in the Australian New Zealand Clinical Trials Registry (ACTRN12617000821392) and commenced recruitment in July 2017. The primary manuscript will be submitted for publication in a peer-reviewed journal.Trial registration numberACTRN12617000821392

The impact of exogenous nitric oxide during cardiopulmonary bypass for cardiac surgery

Perfusion ◽  
2021 ◽  
pp. 026765912110148
Author(s):  
Joseph Mc Loughlin ◽  
Lorraine Browne ◽  
John Hinchion
Keyword(s):  
Nitric Oxide ◽  
Systematic Review ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Troponin I ◽  
Length Of Hospital Stay ◽  
Cochrane Library ◽  
High Quality Research ◽  
Low Cardiac Output Syndrome ◽  
The Impact

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.

scholarly journals Statistical analysis plan for the NITric oxide during cardiopulmonary bypass to improve Recovery in Infants with Congenital heart defects (NITRIC) trial

2021 ◽  
Vol 23 (1) ◽  
pp. 47-58
Author(s):  
Kristen S Gibbons ◽  
◽  
Luregn J Schlapbach ◽  
Kerry Johnson ◽  
Stephen B Horton ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Statistical Analysis ◽  
Cardiopulmonary Bypass ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Statistical Tests ◽  
Heart Defects ◽  
Statistical Analysis Plan ◽  
Statistical Analyses ◽  
Secondary Outcome

Abstract Background: The NITric oxide during cardiopulmonary bypass (CPB) to improve Recovery in Infants with Congenital heart defects (NITRIC) trial, a 1320-patient, multicentre, randomised controlled trial, is aiming to improve survival free of ventilation after CPB by using nitric oxide delivered into the oxygenator of the CPB. Objective: To provide a statistical analysis plan before completion of patient recruitment and data monitoring. Final analyses for this study will adhere to this statistical analysis plan, which details all key pre-planned analyses. Stata scripts for analyses have been prepared alongside this statistical analysis plan. Methods: The statistical analysis plan was designed collaboratively by the chief investigators and trial statistician and builds on the previously published study protocol. All authors remain blinded to treatment allocation. Detail is provided on statistical analyses including cohort description, analysis of primary and secondary outcomes and adverse events. Statistical methods to compare outcomes are planned in detail to ensure methods are verifiable and reproducible. Results: The statistical analysis plan developed provides the trial outline, list of mock tables, and analysis scripts. The plan describes statistical analyses on cohort and baseline description, primary and secondary outcome analyses, process of care measures, physiological descriptors, and safety and adverse event reporting. We define the pre-specified subgroup analyses and the respective statistical tests used to compare subgroups. Conclusion: The statistical analysis plan for the NITRIC trial establishes detailed pre-planned analyses alongside Stata scripts to analyse the largest trial in the field of neonatal and paediatric heart surgery. The plan ensures standards for trial analysis validity aiming to minimise bias of analyses. Trial registration: ACTRN12617000821392

Effects of cardiopulmonary bypass and inhaled nitric oxide on platelets in children with congenital heart defects

1998 ◽  
Vol 157 (3) ◽  
pp. 194-201 ◽  
Author(s):  
J. Breuer ◽  
G. Leube ◽  
P. Mayer ◽  
S. Gebhardt ◽  
L. Sieverding ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cardiopulmonary Bypass ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Heart Defects ◽  
Inhaled Nitric Oxide

Effects of L-citrulline supplementation on nitric oxide and antioxidant markers after high-intensity interval exercise in young men: a randomized controlled trial

2021 ◽  
pp. 1-23
Author(s):  
Kosar Valaei ◽  
Javad Mehrabani ◽  
Alexei Wong
Keyword(s):  
Nitric Oxide ◽  
High Intensity ◽  
Controlled Trial ◽  
Young Men ◽  
No Production ◽  
Double Blind ◽  
Interval Exercise ◽  
Damage Indices ◽  
High Intensity Interval ◽  
Antioxidant Markers

Abstract L-citrulline (L-Cit) is a nonessential amino acid that stimulates nitric oxide (NO) production and improves exercise performance by reducing muscle damage indices; however, the direct benefits of L-Cit on antioxidant markers are unclear. The aim of this study was to examine antioxidant responses to high-intensity interval exercise following acute L-Cit supplementation. Nine young men (21 ± 1 years) participated in a double-blind crossover study in which they received 12 g of L-Cit and placebo (PL) an hour prior to high-intensity interval exercise on two occasions, separated by a seven-day washout period. Blood samples were obtained before (PRE), immediately after (IP), 10 (10P), and 30 min after exercise (30P) from the cubital vein using standard procedures. Serum concentrations of superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and NO metabolites (NOx) were measured. The exercise protocol significantly elevated SOD (p = 0.01) and GPx (p = 0.048) from PRE to 10P in the L-Cit group with greater changes than the PL group. CAT concentrations increased IP (p = 0.014) and remained elevated at 10P (p = 0.03) and 30P (p = 0.015) in both the L-Cit and PL conditions. NOx concentrations increased IP (p = 0.05) in the L-Cit group with greater changes than PL group in PRE to IP, PRE to 10P, and PRE to 30P (p < 0.05). Our data indicate that L-Cit supplementation (single 12 g dose pre-exercise) induces improvements in antioxidant markers following a session of high-intensity interval exercise in young men.

Inhaled nitric oxide and prevention of pulmonary hypertension after congenital heart surgery: a randomised double-blind study

The Lancet ◽  
2000 ◽  
Vol 356 (9240) ◽  
pp. 1464-1469 ◽  
Author(s):  
Owen I Miller ◽  
Swee Fong Tang ◽  
Anthony Keech ◽  
Nicholas B Pigott ◽  
Elaine Beller ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Pulmonary Hypertension ◽  
Congenital Heart ◽  
Heart Surgery ◽  
Congenital Heart Surgery ◽  
Inhaled Nitric Oxide ◽  
Blind Study ◽  
Double Blind Study ◽  
Double Blind

scholarly journals Impact of an Herbal Dietary Supplement Containing Spilanthes acmella and Orchis latifolia on Testosterone in Young Men

2016 ◽  
Vol 8 (1) ◽  
pp. 28
Author(s):  
Ryan G. Moran ◽  
Alex T. VonSchulze ◽  
Richard J. Bloomer
Keyword(s):  
Nitric Oxide ◽  
Young Men ◽  
Moderate Increase ◽  
Herbal Preparation ◽  
Double Blind ◽  
Total Blood ◽  
Blood Samples ◽  
Healthy Men ◽  
Spilanthes Acmella ◽  
The Impact

Attention has been given recently to herbal dietary supplements proposed to elevate testosterone and nitric oxide. This study evaluated the impact of a supplement containing Spilanthes acmella extract and Orchis latifolia extract on total blood testosterone, cortisol, and nitrate/nitrite in healthy men. Methods: Thirteen men (25.0±1.0 years) were randomly assigned (double-blind, cross-over design) to ingest a supplement (containing Spilanthes acmella extract and Orchis latifolia extract) and a placebo daily for 14 days, with a 14-day washout period between assignments. Fasting blood samples were collected on the mornings of days 1, 4, 8, and 15 and analyzed for testosterone, cortisol, and nitrate/nitrite. On day 15, subjects ingested an acute dose of the supplement or placebo and blood was collected every 30 minutes for three hours, and analyzed for testosterone. Results: No increase of significance was noted for any biochemical variable (p>0.05). However, a mean increase in testosterone from day 1 to day 15 of 29% was observed for the 13 subjects when ingesting the supplement, with a mean increase of 56% noted when only considering the 8 subjects who “responded” to treatment. Cortisol was increased approximately 19% when subjects ingested the supplement, compared to only 9% with the placebo. Conclusion: Two weeks of supplementation with an herbal preparation containing Spilanthes acmella extract and Orchis latifolia extract can increase testosterone in selected young men. The supplement also results in a moderate increase in cortisol. Larger scale studies are needed to further evaluate the impact of this herbal combination on testosterone in men.

Time Course of Endothelin-1 and Nitrate Anion Levels After Cardiopulmonary Bypass in Congenital Heart Defects

1997 ◽  
Vol 63 (3) ◽  
pp. 648-652 ◽  
Author(s):  
Takeshi Hiramatsu ◽  
Yasuharu Imai ◽  
Yoshinori Takanashi ◽  
Shuichi Hoshino ◽  
Masafumi Yashima ◽  
...  
Keyword(s):  
Cardiopulmonary Bypass ◽  
Congenital Heart Defects ◽  
Congenital Heart ◽  
Time Course ◽  
Heart Defects ◽  
Nitrate Anion ◽  
Endothelin 1

scholarly journals Ropivacaine 75mg versus placebo in perineal infiltration for analgesic efficacy at mid- and long-term for episiotomy repair in postpartum women- The ROPISIO study: a two-center, randomized, double-blind, placebo-controlled trial.

2020 ◽  
Author(s):  
Claire CARDAILLAC ◽  
Stéphane Ploteau ◽  
Aurélie Le Thuaut ◽  
Vincent Dochez ◽  
Norbert Winer ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Controlled Trial ◽  
Analgesic Efficacy ◽  
Perineal Pain ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Mediolateral Episiotomy ◽  
The Impact

Abstract Background Perineal pain due to episiotomy is commonly reported and can be severe enough to disturb the mother-infant dyad during the postpartum period. Its incidence at day 7 postpartum varies from 63% to 74%. Recent studies have already investigated the analgesic efficacy of perineal infiltration of ropivacaine after episiotomy, but have only focused on the immediate postpartum period (at 24 and 48 hours after birth). Large, adequately powered, multicenter, randomized controlled trials are required to evaluate the impact of ropivacaine infiltration on perineal pain and mid- and long-term quality of life before the widespread use of ropivacaine to prevent perineal pain after episiotomy can be recommended. Methods The ROPISIO study is a two-center, randomized, double-blind, placebo-controlled trial in La Roche sur Yon and Nantes, France. It will involve 272 women with vaginal singleton delivery and mediolateral episiotomy at term (≥ 37 weeks). Perineal infiltration (ropivacaine 75mg or placebo) will be administrated just after vaginal birth and before episiotomy repair. The primary outcome will be the analgesic efficacy at day 7 postpartum (mid-term), defined by the numerical rating scale of pain (ENS NRS) strictly superior to 3/10 on the perineal repair area. Secondary outcomes will be the analgesic efficacy (ENS NRS), the impact of pain on daily behavior, on the quality of life (36-Item Short Form Health Survey), on the occurrence of symptoms of postpartum depression (Edinburgh Postnatal Depression Scale) and on sexuality (Female Sexual Function Index) at 3 and 6 months (long-term) using validated online questionnaires. This study will have 90% power to show approximately 30% relative risk reduction in the incidence of perineal pain at day 7, from 70.0% to 50.0%. Discussion Ropivacaine is a promising candidate drug, inexpensive, easy to administer, and would be suitable to include in the routine management of deliveries in labor ward. This study will investigate if perineal ropivacaine infiltration just after birth can reduce mid- and long-term postpartum pain and increase quality of life in women with mediolateral episiotomy.

scholarly journals Treatment of systemic inflammatory response syndrome following on-pump pediatric congenital heart surgery

2021 ◽  
Vol 10 (2) ◽  
pp. 113-124
Author(s):  
D. V. Borisenko ◽  
A. A. Ivkin ◽  
D. L. Shukevich
Keyword(s):  
Cardiopulmonary Bypass ◽  
Systemic Inflammatory Response Syndrome ◽  
Inflammatory Response ◽  
Congenital Heart ◽  
Heart Surgery ◽  
Heart Defects ◽  
Surgical Techniques ◽  
Congenital Heart Surgery ◽  
Systemic Inflammatory Response ◽  
Preventive Strategies

Highlights. The article discusses the pathophysiological aspects of cardiopulmonary bypass and the mechanisms underlying the development of the systemic inflammatory response in children following congenital heart surgery. We summarize and report the most relevant preventive strategies aimed at reducing the systemic inflammatory response, including both, CPB-related methods and pharmacological ones.The growing number of children with congenital heart defects requires the development of more advanced technologies for their surgical treatment. However, cardiopulmonary bypass is required in almost all surgical techniques. Despite the tremendous progress and recent advances in cardiopulmonary bypass techniques, the systemic inflammatory response syndrome associated with these surgeries remains unresolved. The review summarizes the causes and mechanisms underlying its development. The most commonly used preventive strategies are reported, including standard and modified ultrafiltration, leukocyte filters, and pharmacological agents (systemic glucocorticoids, aprotinin, and antioxidants).The role of cardioplegia and hypothermia in the reduction of systemic inflammation is defined. Cardiac surgery centers around the world use a variety of techniques and pharmacological approaches, drawing on the results of randomized clinical studies. However, there are no clear and definite clinical guidelines aimed at reducing the systemic inflammatory response during cardiopulmonary bypass in children. It remains a significant problem for pediatric intensive care by aggravating their postoperative status, prolonging the length of the in-hospital stay, and reducing the survival rates.

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