Please select the eligibility criteria that correspond to the clinical trial below.
Title: Volatile Anesthetics to Reduce Mortality in Cardiac Surgery: A Multicentre Randomized Controlled Study
Brief Summary: 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).


Options:
A: Enrollment Inclusion Criteria:

* Age \> 18 years
* Undergoing heart surgery for coronary artery bypass (on-pump or off-pump CABG) and/or valve repair or replacement (excluding mechanical valves), including re-operations
* Hemodynamically stable

Randomization Inclusion Criteria

* AF that persists for \> 60 minutes or recurrent (more than one) episodes of AF up to 7 days after surgery during the index hospitalization.

Exclusion Criteria:

* LVAD insertion or heart transplantation
* Maze procedure
* TAVR
* History of or planned mechanical valve replacement
* Correction of complex congenital cardiac defect (excluding bicuspid aortic valve, atrial septal defect or PFO)
* History of AF or AFL
* History of AF or AFL ablation
* Contraindications to warfarin or amiodarone
* Need for long-term anticoagulation
* Concurrent participation in an interventional (drug or device) trial
B: Inclusion Criteria:

* patients underwent isolated or combined coronary artery bypass grafting and/or surgical treatment for heart valve diseases

Exclusion Criteria:

* none
C: 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)
D: Inclusion Criteria:

* hospitalized in intensive care unit for less than 7 days
* septic shock for less than 24 hours
* at least one proven site of infection
* at least 2 organ dysfunction as defined by a SOFA score =or\> to 3 for at least 6 consecutive hours
* need for vasopressor (dopamine =or\>15µg/kg/min or epinephrine/norepinephrine at =or\>0,25 µg/kg/min for at least 6 consecutive hours, to maintain systolic arterial pressure at 90 mmHg or more OR mean arterial pressure at 6( mmHg or more
* informed consent

Exclusion Criteria:

* pregnancy or breath feeding
* decision not to resuscitate
* underlying disease with an estimated life expectancy of less than 1 month
* formal indication for corticosteroids
* recent surgery (ie within the past 72 hours) or a surgery at high risk of bleeding
* gastro-intestinal bleeding within the past 6 weeks
* chronic liver disease (Child C)
* recent trauma (ie within the past 72 hours)
* intracranial process
* history of stroke, CNS bleeding or traumatic brain injury within the past 3 months
* platelet counts of less than 30000 per cubic millimeter
* formal indication for curative anticoagulant; prophylactic use of heparin is allowed
* any condition of high risk of bleeding as per patient's primary physicians
* hypersensitivity of activated drotrecogin alpha or any other component of the drug
* no affiliation to a social security

Amendments to eligibility criteria were:

On 27/03/2008: Changes in following exclusion criteria :

* "surgical procedure in the past 7 days" was changed for "surgical procedure within 72 hours, or any surgery associated with high risk of bleeding, or a planned surgery within 24 h".
* "chronic liver disease" was clarified as "chronic liver disease with Child score C".
* "severe thrombopenia" was clarified "as severe thrombopenia (\<30,000/mm3, before transfusion).

On 25/08/2009: The exclusion criteria: surgical procedure within 72 hours, or any surgery associated with high risk of bleeding, or a planned surgery within 24 h" was changed for "surgical procedure within 12 hours, or any surgery associated with high risk of bleeding

On 11/06/2010: the inclusion criteria: admitted to the ICU for \< 7 days was removed; and a new exclusion criteria was added: "patients who had a previous episode of sepsis during the same hospital stay

On 18/04/2012: following the withdrawal of DAA from the market: the following exclusion criteria (only related to DAA) were removed :

1. any surgery in the past 12 hours, or any surgery associated with high risk of bleeding;
2. chronic liver disease with a Child score C;
3. recent trauma;
4. any intracranial mass, or stroke or head injury in the past 3 months;
5. severe thrombocytopenia (\< 30.000 /mm3, before platelet transfusion);
6. formal indication for anticoagulation, or any other condition associated with increased risk of bleeding, as appreciated by the patient's physician.

Answer: C