Volatile Anesthetics to Reduce Mortality in Cardiac Surgery (MYRIAD)

Volatile Anesthetics to Reduce Mortality in Cardiac Surgery: A Multicentre Randomized Controlled Study

There is initial evidence that the choice of anesthesia can influence survival in the specific setting of coronary artery bypass grafting surgery (CABG).

A recent international consensus conference included volatile agents among the few drugs/techniques/strategies that might reduce perioperative mortality in cardiac surgery and that should be further studied. Volatile anesthetics (desflurane, isoflurane and sevoflurane) have non-anesthetic pharmacological characteristics that confer cardiac protection when compared to Total IntraVenous Anesthesia (TIVA). Several randomized controlled studies were summarized in a meta-analysis that documented a reduction in perioperative cardiac troponin release and mortality in patients receiving volatile anesthetics when compared to patients receiving a TIVA. There are four published studies (Bignami et al. 2009) (De Hert et al. 2009) (Jackobsen et al. 2007) (Landoni et al. 2007) suggesting that these benefits can translate into a reduced mortality rate in patients receiving volatile agents. The level of evidence for these four studies is not high (one meta-regression, one underpowered randomized controlled study, one retrospective study and one meta-analysis of small randomized studies) and there is need for a large multicentre randomized controlled study to confirm these findings, as suggested by the international consensus conference on this topic published in 2011 (Landoni et al 2011).

The purpose is to provide a large multicentre controlled randomized trial to demonstrate that volatile anesthetics can reduce 1 year mortality from 3% to 2% in patients undergoing CABG (either with or without cardiopulmonary bypass).

The results of this study can support the use of volatile agents in all CABG procedures worldwide (more than 500.000 per year) with 2.500 lives saved per year (in the hypothesis that nowadays half the procedures are performed with a TIVA and that 1 year mortality can be reduced from 3% to 2% using volatile agents).

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery; Coronary Artery Bypass Grafting; Aortocoronary Bypass
• Intervention / Treatment: Drug: desflurane, isoflurane, sevoflurane; Drug: total intravenous anesthetics

• Study Type: Interventional
• Enrollment (Actual): 5400
• Phase: Phase 4

Contacts and Locations

Study Locations

• Bahrain
  • Bahrein, Bahrain
    • Mohammed Bin Khalifa Bin Sulman Al-Khalifa Cardiac Center - Bahrain
• Brazil
  • Sao Paulo, Brazil
    • Dante Pazzanese Institute of Cardiology
  • Barazil
    • Sao Paulo, Barazil, Brazil
      • Hospital das Clínicas da Faculdade de Medicina da USP - Istituto do Coracao
• Bulgaria
  • Burgas, Bulgaria
    • Heart Center Pontica
• China
  • Beijing, China
    • Beijing Anzhen Hospital, Capital Medical University
  • Changsha, China
    • The second Xiangya hospital of central south university
  • Hubei, China
    • Wuhan Asia Heart Hospital
  • Xi'an, China
    • 1st Affiliated Hospital of Fourth Military University
• Croatia
  • Dubrava, Croatia
    • University Hospital Dubrava
• Czechia
  • Czech Republic
    • Prague, Czech Republic, Czechia
      • General University Hospital, Charles University
    • Prague, Czech Republic, Czechia
      • Institute for Clinical and Experimental Medicine
• Egypt
  • Egypt, Egypt
    • Mansoura university hospitals
  • Zagazig, Egypt
    • Faculty of Medicine - Zagazig University
• Italy
  • Bologna, Italy
    • Policlinico San Orsola-Malpighi
  • Brescia, Italy
    • Spedali Civili
  • Catanzaro, Italy
    • Policlinico Universitario Magna Graecia
  • Milano, Italy, 20132
    • Ospedale San Raffaele di Milano, Italy
  • Milano, Italy
    • Humanitas
  • Padova, Italy
    • Azienda Ospedaliera di Padova
  • Roma, Italy
    • Policlinico Universitario Campus Biomedico
  • Roma, Italy
    • Azienda Ospedaliera San Camillo-Forlanini
  • Torino, Italy
    • AOU Città della Salute e della Scienza
• Malaysia
  • Lumpur, Malaysia
    • Hospital Serdang
  • Lumpur, Malaysia
    • University Malaya Medical Centre
  • Penang, Malaysia
    • Hospital Pulau Pinang
  • Sarawak, Malaysia
    • Sarawak General Hospital
• Portugal
  • Lisbon, Portugal
    • Hospital Santa Maria
• Russian Federation
  • Astrakhan, Russian Federation
    • Federal Centre for Cardiac Surgery
  • Ekaterinburg, Russian Federation
    • Ural Institute of Cardiology
  • Kemerovo, Russian Federation
    • Scientific Research Institute for Complex Issues of Cardiovascular Disease
  • Moscow, Russian Federation
    • Moscow Clinical Regional Research Institute
  • Moscow, Russian Federation
    • Negovskiy Reanimatology Research Institute
  • Novosibirsk, Russian Federation
    • State Research Institute of Circulation Pathology
  • Saint Petersburg, Russian Federation
    • Federal Almazov Medical Research Centre
• Saudi Arabia
  • Mecca, Saudi Arabia
    • King Abdullah Medical City - KAMC
• Serbia
  • Belgrade, Serbia
    • Institute of Cardiovascular Diseases "Dedinje"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• age >18 years
• written informed consent
• scheduled procedures
• planned isolated CABG (multiple bypass are allowed; planned combined intervention such as CABG plus valve surgery are not allowed

Exclusion Criteria:

• pregnancy
• planned valve surgery or surgery on the aorta
• planned locoregional anesthesia without general anesthesia
• unstable or ongoing angina
• recent (< 1 month) or ongoing acute myocardial infarction
• use of sulfonylurea, theophylline or allopurinol
• previous unusual response to an anesthetic agent
• inclusion in other randomised controlled studies in the previous 30 days
• any general anesthesia performed in the previous 30 days
• emergency operation (not scheduled)
• Kidney or liver transplant in medical history
• Liver cirrhosis (Child B or C)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: volatile anesthetics (desflurane, isoflurane, sevoflurane)	Drug: desflurane, isoflurane, sevoflurane
Active Comparator: total intravenous anesthesia	Drug: total intravenous anesthetics

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
mortality	1 year

Collaborators and Investigators

• Sponsor: Università Vita-Salute San Raffaele
• Investigators: Study Chair: Alberto Zangrillo, Prof, Vita-Salute University of Milano

Publications and helpful links

General Publications

• Landoni G, Greco T, Biondi-Zoccai G, Nigro Neto C, Febres D, Pintaudi M, Pasin L, Cabrini L, Finco G, Zangrillo A. Anaesthetic drugs and survival: a Bayesian network meta-analysis of randomized trials in cardiac surgery. Br J Anaesth. 2013 Dec;111(6):886-96. doi: 10.1093/bja/aet231. Epub 2013 Jul 12.
• Landoni G, Rodseth RN, Santini F, Ponschab M, Ruggeri L, Szekely A, Pasero D, Augoustides JG, Del Sarto PA, Krzych LJ, Corcione A, Slullitel A, Cabrini L, Le Manach Y, Almeida RM, Bignami E, Biondi-Zoccai G, Bove T, Caramelli F, Cariello C, Carpanese A, Clarizia L, Comis M, Conte M, Covello RD, De Santis V, Feltracco P, Giordano G, Pittarello D, Gottin L, Guarracino F, Morelli A, Musu M, Pala G, Pasin L, Pezzoli I, Paternoster G, Remedi R, Roasio A, Zucchetti M, Petrini F, Finco G, Ranieri M, Zangrillo A. Randomized evidence for reduction of perioperative mortality. J Cardiothorac Vasc Anesth. 2012 Oct;26(5):764-72. doi: 10.1053/j.jvca.2012.04.018. Epub 2012 Jun 20.
• Landoni G, Lomivorotov V, Pisano A, Nigro Neto C, Benedetto U, Biondi Zoccai G, Gemma M, Frassoni S, Agro FE, Baiocchi M, Barbosa Gomes Galas FR, Bautin A, Bradic N, Carollo C, Crescenzi G, Elnakera AM, El-Tahan MR, Fominskiy E, Farag AG, Gazivoda G, Gianni S, Grigoryev E, Guarracino F, Hanafi S, Huang W, Kunst G, Kunstyr J, Lei C, Lembo R, Li ZJ, Likhvantsev V, Lozovskiy A, Ma J, Monaco F, Navalesi P, Nazar B, Pasyuga V, Porteri E, Royse C, Ruggeri L, Riha H, Santos Silva F, Severi L, Shmyrev V, Uvaliev N, Wang CB, Wang CY, Winterton D, Yong CY, Yu J, Bellomo R, Zangrillo A. MortalitY in caRdIAc surgery (MYRIAD): A randomizeD controlled trial of volatile anesthetics. Rationale and design. Contemp Clin Trials. 2017 Aug;59:38-43. doi: 10.1016/j.cct.2017.05.011. Epub 2017 May 19.
• Landoni G, Lomivorotov VV, Nigro Neto C, Monaco F, Pasyuga VV, Bradic N, Lembo R, Gazivoda G, Likhvantsev VV, Lei C, Lozovskiy A, Di Tomasso N, Bukamal NAR, Silva FS, Bautin AE, Ma J, Crivellari M, Farag AMGA, Uvaliev NS, Carollo C, Pieri M, Kunstyr J, Wang CY, Belletti A, Hajjar LA, Grigoryev EV, Agro FE, Riha H, El-Tahan MR, Scandroglio AM, Elnakera AM, Baiocchi M, Navalesi P, Shmyrev VA, Severi L, Hegazy MA, Crescenzi G, Ponomarev DN, Brazzi L, Arnoni R, Tarasov DG, Jovic M, Calabro MG, Bove T, Bellomo R, Zangrillo A; MYRIAD Study Group. Volatile Anesthetics versus Total Intravenous Anesthesia for Cardiac Surgery. N Engl J Med. 2019 Mar 28;380(13):1214-1225. doi: 10.1056/NEJMoa1816476. Epub 2019 Mar 19.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2014
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: April 2, 2014
• First Submitted That Met QC Criteria: April 4, 2014
• First Posted (Estimate): April 7, 2014

Study Record Updates

• Last Update Posted (Actual): April 2, 2019
• Last Update Submitted That Met QC Criteria: March 29, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: cardiac surgery; anesthesia; sevoflurane; TIVA; intensive care; mortality; desflurane; isoflurane; volatile anesthetics
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Platelet Aggregation Inhibitors; Anesthetics, Inhalation; Anesthetics; Desflurane; Sevoflurane; Isoflurane; Anesthetics, Intravenous
• Other Study ID Numbers: VOLATILE/38/OSR