Type A aortic dissection is a surgical emergency associated with high morbidity and mortality. Cardiac surgery with cardiopulmonary bypass triggers a complex sequence of events leading to the activation of both pro- and anti-inflammatory mediators, resulting in a systemic inflammatory response syndrome (SIRS) that may contribute to postoperative complications. Several mechanisms, such as blood contact with the extracorporeal circuit components, ischemia-reperfusion injury, endotoxemia, and surgical trauma, have been identified as potential triggers of this inflammatory response.

Over the years, different strategies have been developed to minimize the impact of postoperative SIRS, including improvements in the materials used in extracorporeal circuits and surgical techniques. However, due to the complexity of its pathophysiology, there is still no clear management strategy. Glucocorticoids are potent immunomodulators that have been studied in the context of cardiac surgery, mainly focusing on high-dose prophylactic administration during cardiopulmonary bypass, but without demonstrating a reduction in postoperative mortality to date.

This study compares the administration of intravenous methylprednisolone for three days in the immediate postoperative period of type A aortic dissection with standard treatment. The study aimed to explore the potential benefits of glucocorticoid (GC) administration in reducing systemic inflammation and consequently mitigating organ dysfunction.

The primary endpoint was the reduction in the Sequential Organ Failure Assessment (SOFA) score on postoperative day 4 compared to baseline (postoperative day 1 before methylprednisolone administration). The secondary endpoints included in-hospital mortality, intensive care unit (ICU) and hospital length of stay, duration of mechanical ventilation, need for renal replacement therapy, neurological complications, and levels of inflammatory markers.

Patients older than 18 years with a confirmed diagnosis of type A aortic dissection by computed tomography angiography who underwent surgical treatment and had a life expectancy of more than three days were included in the study. Exclusion criteria comprised contraindications to glucocorticoid administration, prior glucocorticoid use within 14 days before surgery, and iatrogenic aortic dissection.

A total of 212 patients were randomized to receive either glucocorticoids or standard treatment (106 patients per group). The glucocorticoid group received intravenous methylprednisolone for three days following surgery. The dosing regimen was as follows:

• Day 1: 1 mg/kg every 12 hours (total: 2 mg/kg/day)
• Day 2: 0.5 mg/kg every 12 hours (total: 1 mg/kg/day)
• Day 3: 0.25 mg/kg every 12 hours (total: 0.5 mg/kg/day)

Both groups received a single 5 mg dose of dexamethasone during anesthetic induction to prevent postoperative nausea and vomiting. The postoperative use of glucocorticoids (except for the prescribed doses in the glucocorticoid group) was prohibited in both groups, except in life-threatening emergencies such as anaphylactic shock.

Significant differences were found in favor of the glucocorticoid group:

• Reduction in SOFA score: 3.16 ± 2.52 in the control group vs. 4.36 ± 2.82 in the glucocorticoid group. No initial differences in SOFA score were observed between groups. The benefit of SOFA reduction was more pronounced in patients with higher baseline APACHE scores and elevated C-reactive protein (CRP) levels.
• Marked reduction in C-reactive protein (CRP) levels in the glucocorticoid group compared to the control group (91 mg/dL vs. 182 mg/dL).
• Lower need for continuous renal replacement therapy in the glucocorticoid group (8.5% vs. 19.8%).
• No significant differences in in-hospital mortality, ICU or hospital length of stay, duration of mechanical ventilation, or neurological complications between groups.
• Infection rates were similar between groups. However, blood glucose levels were higher in the glucocorticoid group.

The main limitations of the study included the open-label design and the fact that it was not powered to evaluate mortality or long-term outcomes. Additionally, the impact of glucocorticoid-induced hyperglycemia and other potential side effects, such as electrolyte imbalances or neuropsychiatric effects, were not assessed.

The authors concluded that postoperative glucocorticoid administration in patients with type A aortic dissection significantly reduces postoperative inflammation and improves early postoperative organ dysfunction.

COMMENTARY:

Type A aortic dissection remains a challenging condition in which emergency surgical treatment—typically ascending aorta replacement—is the therapy of choice. Medical management aimed at controlling heart rate, blood pressure, and pain plays a crucial role in reducing wall stress and attempting to limit false lumen pressurization and propagation. However, despite advancements in surgical techniques, anesthetic management, and postoperative care, complication and mortality rates remain high. Cardiopulmonary bypass and the surgical procedure itself can trigger a SIRS, leading to postoperative complications. This response occurs through the activation of inflammatory mediators, endotoxins, coagulation cascades, and complement systems, ultimately increasing endothelial permeability and causing organ dysfunction. The magnitude of this inflammatory response varies significantly among individuals.

Glucocorticoids have been proposed in this context to attenuate the body’s inflammatory response, but their use remains controversial due to conflicting evidence. Glucocorticoids are potent anti-inflammatory and immunosuppressive agents widely used in clinical practice. Studies have demonstrated their ability to significantly reduce proinflammatory cytokine concentrations and endotoxin release. However, their use—especially in chronic settings—is associated with significant adverse effects, including osteoporosis, hyperglycemia, insulin resistance, altered fat distribution, hypertension, and long-term muscle atrophy, as well as short-term risks such as gastrointestinal bleeding and infection. The treatment of various acute and chronic inflammatory diseases requires tailored glucocorticoid strategies, as their side effects are dose-dependent. Therefore, it is crucial to find an optimal therapeutic dose in each clinical scenario to maximize benefits while minimizing adverse effects.

Most clinical trials in the context of cardiac surgery, including the DECS and SIRS studies, have focused on glucocorticoid administration during anesthetic induction or cardiopulmonary bypass. These trials have used variable doses and different glucocorticoid agents but have not demonstrated a reduction in postoperative mortality or major complications. However, glucocorticoid use has been associated with higher blood glucose levels, though the clinical consequences of this remain unclear. The DECS study suggested improved pulmonary function, as glucocorticoid administration was associated with shorter mechanical ventilation duration and ICU stay. Conversely, the SIRS study reported an increased risk of perioperative myocardial injury/infarction with glucocorticoid use, though this finding was not observed in other trials—likely due to the heterogeneity in defining perioperative infarction. In the SIRS study, myocardial injury was assessed solely based on CK-MB levels. Additionally, some studies suggest that glucocorticoids may reduce the incidence of postoperative atrial fibrillation. Importantly, no increased risk of infection or gastrointestinal bleeding has been reported in patients receiving glucocorticoids in these studies.

The article under discussion differs from previous literature in that glucocorticoid administration was initiated in the immediate postoperative period rather than during surgery, and the doses used were higher than in most previous studies. The authors extrapolated the glucocorticoid doses from acute respiratory distress syndrome (ARDS) treatment protocols, based on prior observations suggesting potential pulmonary function benefits. The study population included only patients with type A aortic dissection, excluding those with ischemic heart disease, who might experience worse outcomes with glucocorticoid therapy.

To date, glucocorticoids have not demonstrated a mortality benefit in cardiac surgery. However, they appear to reduce pulmonary complications while possibly increasing cardiac complications, without significantly elevating infection risk. The evidence supporting these findings remains limited. Other potential consequences, such as hyperglycemia and neuropsychiatric complications with high-dose glucocorticoids, require further clarification.

Given these uncertainties, future studies should aim to identify patients at higher risk of developing a severe inflammatory response to individualize glucocorticoid therapy, as routine use in postoperative SIRS cannot yet be recommended. Nevertheless, glucocorticoids may have a role in selected cases, requiring careful risk-benefit assessment. Critical aspects that remain unresolved include the ideal glucocorticoid agent, optimal timing of administration, and minimum effective dose that minimizes adverse effects. Several ongoing studies (MEDAL, DECS-II) are expected to provide further insights into this decades-long controversy.

REFERENCE:

Luo M-H, Luo J-C, Xu X, He Z-H, Huang Y-R, Chen C et al. Effects of postoperative glucocorticoids on mitigation of organ dysfunction in patients with type A aortic dissection: a randomized controlled trial. Eur J Cardiothorac Surg. 2024; 66(6).