Efficacy of low-dose hydrocortisone in vasoplegic shock after cardiac surgery: a randomized clinical trial

• Grant number: 21/00133-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2021
• Effective date (End): September 30, 2022
• Field of knowledge: Health Sciences - Medicine - Surgery
• Principal Investigator: Filomena Regina Barbosa Gomes Galas
• Grantee: Vinícius Alcantara de Oliveira Costa
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Systemic Inflammatory Response Syndrome (SIRS) resulting from surgical trauma and enhanced by cardiopulmonary bypass (CPB) is often associated with increased endothelial and vascular permeability, as well as increased cardiac ischemic events, multiorgan dysfunctions, severe hemorrhagic events, and death. Severe SIRS, associated with significant hypotension in the postoperative period of cardiac surgery, is called vasoplegic syndrome (VS), and occurs in about 5 to 25% of patients, being considered a common complication. VS, characterized by hypotension with normal or increased cardiac output and low systemic vascular resistance, increases the need to use fluids and vasopressors during the perioperative period. Most studies on the treatment of SIRS come from studies on sepsis and septic shock. Randomized studies have attempted to evaluate the use of corticosteroids as an adjuvant treatment in these conditions. In this context, studies from the '90s showed that the use of low doses of hydrocortisone reduced the time of use of vasopressors. Thus, knowing that VS is often associated with perioperative complications, the use of corticosteroids is interesting because it is an affordable, low-cost treatment and associated with few side effects when used in low doses and for a short period. The present study aims to evaluate, through a prospective and randomized clinical study, whether the use of low doses of hydrocortisone reduces the severity of organ dysfunction (assessed using the delta SOFA score) resulting from VS in the postoperative (PO) period of cardiac surgery. The primary objective is to evaluate the efficacy of corticosteroids on vasopressor-free days. Secondary objectives include assessing (in 30 days): mortality; length of stay in the ICU; acute kidney injury; sepsis; myocardial ischemia; atrial fibrillation. Still, other outcomes will be evaluated, such as 6-month mortality; levels of inflammatory markers (IL1, IL6, IL8, IL10, TNFalpha) after randomization, 24 hours and 48 hours; total, free cortisol and ACTH measurement (after randomization, 24 hours and 48 hours); daily levels of tissue perfusion parameters until the 3rd PO or discharge from the ICU and hemodynamics assessment in 48 hours of ICU; among other pertinent outcomes. It is also important to note that for each of the complications and outcomes, there are well-defined definitions and parameters to be assessed. Patients over 18 years of age, that made use of noradrenaline> 0.1 mcg/kg/min to adjust the BP for at least 30 min within 24 hours of the PO undergoing cardiac surgery with CPB at the Heart Institute (InCor) of the Medical School of USP, will be consecutively included. Exclusion criteria include aorta surgery, transplantation, congenital heart disease, and endocarditis; gestation; infection in the last 30 days; neoplasms; among other pertinent criteria. We hypothesize that the steroid increases the vasopressor free time by 1 day compared to the use of a placebo (SD = 2). Thus, the sample size calculated with statistical power was 140 patients, considering possible losses in 10%. The CPB technique, the surgical and anesthetic procedures will be standardized. Patients will be randomized, within the first 24h of PO for one of the groups, in a 1: 1 ratio. The hydrocortisone group will receive 200mg of the steroid diluted in 120ml, and the control group will receive a 0.9% saline solution. Both in a continuous infusion, 5ml / h for 3 days or until the shock is reversed. All concomitant treatments will be accepted except anti-inflammatory drugs and corticosteroids for 28 days. Protocol deviation: Control group patients who evolve with a clinical indication for corticosteroids will be able to receive treatment and will be analyzed according to the intention to treat principle.(AU)