Cardiac surgery is a high-risk surgery and is associated with a rate of postoperative adverse outcomes. Like many others major surgery, cardiac surgery procedures induce a proinflammatory phase usually counterbalanced with an immunosuppressive phase so the immune response remained balanced.
In some cases, the immune response might be dysregulated with a more pronounced pro inflammatory state that compromises organ perfusion and with the occurrence of organ failure. From a mechanistic approach, the relationship between organ failure is complex and multifactorial with a high level of proinflammatory cytokines, a decrease in microcirculation, an endothelial dysfunction and an activation of coagulation and over. The clinical expression is an increase in vasopressor exposure and dose, an increase in mortality and in adverse outcomes with a predominance of acute kidney injury.
Various therapies have been assessed to manage cardiac surgery related sepsis including glucocorticoid therapy. Briefly, two major randomized trials assessed glucocorticoid therapy solely in scheduled cardiac surgery with cardiopulmonary bypass. No clinical benefit was demonstrated in term of reduction in postoperative mortality or adverse outcomes. Since, data support that the selection of patients at risk is crucial to demonstrate such a strategy. Indeed, data support that surprisingly some patients will have a very light immune response reflected by a low pro inflammatory cytokine.
The hypothesis is that the combination glucocorticoid and fludrocortisone could decrease adverse outcomes in selected patients.
Age > 18 years.
Patient at intermediate/high risk (EuroSCORE II > 4%).
Coronary artery bypass grafting (CABG).
Aortic valve replacement.
Endocarditis
Off-pump heart surgery
Heart transplantation or long-term ventricular assist device (VAD)
Emergency surgery: aortic dissection, emergency coronary artery bypass grafting (CABG)
Parallel
hydrocortisone plus fludrocortisone
Drug* Hydrocortisone 200 mg/day for 5 days or until ICU discharge, starting at the initiation of cardiopulmonary bypass (CPB), administered intravenously via syringe pump in a double-blind manner * Fludrocortisone 50 µg/day in the morning for 5 days or until ICU discharge, administered orally or via nasogastric tube (if the patient is sedated), diluted in a glass of water, in a double-blind manner
placebo of hydrocortisone plus fludrocortisone
Drug* Placebo for hydrocortisone (0.9% NaCl) administered following the same protocol as fludrocortisone in the intervention group * Placebo for fludrocortisone (capsule containing microcrystalline cellulose diluted in a glass of water) administered following the same protocol as fludrocortisone in the intervention group
Variation of acute kidney injury occurence between both groups
Variation of postoperative pulmonary complication occurrence between both groups
Variation of number of norepinephrine requirement between both groups
variation of postoperative atrial fibrillation occurence between both groups
Postoperative atrial fibrillation: defined as a new-onset arrhythmia within 7 days after surgery, documented by an electrocardiogram showing absence of P waves and narrow, irregular QRS complexes
variation of myocardial infarction occurence between both groups
Myocardial infarction: defined according to the Fourth Universal Definition
variation of stroke occurence between both groups
Stroke: defined as the sudden onset of a neurological deficit confirmed by brain imaging
Variation of total amount of norepinephrine between both groups
The total amount of norepinephrine will be expressed in milligrams and will correspond to the cumulative dose administered from ICU admission until the 7th postoperative day.
Click on the lead sponsor to view all of their trials.
Centre Hospitalier Universitaire, Amiens
Lead sponsor
University Hospital, Rouen
Collaborator
University Hospital, Lille
Collaborator
