The Takeaway

Combining dexmedetomidine and hydrocortisone effectively reduces POAF incidence after CABG, with manageable side effects

Study Design

• Prospective, double-blind randomized controlled trial
• 248 patients undergoing elective on-pump CABG
• ASA physical status II and III
• Inclusion criteria: patients undergoing primary, isolated, elective, on-pump surgical revascularization for coronary artery disease
• Exclusion criteria: history of heart block, pacemaker insertion, preoperative AF or flutter, ventricular arrhythmias, uncontrolled diabetes mellitus (HbA1c >8 gm/dL), a history of peptic ulcer, or active systemic bacterial or mycotic infection
• Primary Outcome: occurrence new episode AF within seven days postop

Physiology Refresh

Dexmedetomidine is a selective alpha-2 adrenergic receptor agonist that exerts its primary effects by activating receptors in the locus coeruleus of the brainstem, leading to inhibition of norepinephrine release. This results in sedation, anxiolysis, and analgesia without significant respiratory depression. Its anti-inflammatory properties are mediated through the suppression of sympathetic outflow, which dampens the systemic inflammatory response by reducing cytokine release—particularly TNF-α, IL-6, and IL-1β—making it useful in critical care and surgical settings for blunting the stress response.

Hydrocortisone, a glucocorticoid, penetrates cell membranes and binds to glucocorticoid receptors. It downregulates the transcription of pro-inflammatory genes and upregulates anti-inflammatory proteins like lipocortin-1, which inhibits phospholipase A2, thereby decreasing the synthesis of arachidonic acid-derived mediators such as prostaglandins and leukotrienes. It exerts potent anti-inflammatory action, stabilizes lysosomal membranes, and reduces capillary permeability, contributing to its critical role in managing systemic inflammation, adrenal insufficiency, and septic shock.

Inflammation contributes to atrial fibrillation (AF) by promoting both electrical and structural remodeling of the atrial myocardium. Pro-inflammatory cytokines such as IL-6, TNF-α, and CRP increase oxidative stress, which can trigger and sustain arrhythmogenic foci. Additionally, inflammation promotes fibroblast activation and atrial fibrosis, disrupting the uniform conduction of electrical impulses and creating a substrate for reentry circuits. This pro-arrhythmic environment lowers the threshold for AF initiation and persistence, linking systemic or local inflammation—such as post-surgical states, infections, or chronic inflammatory diseases—to increased AF risk.

Abstract

Objective: Postoperative atrial fibrillation (POAF) occurs in 20%-40% of patients following coronary artery bypass grafting (CABG), contributing to significant morbidity. POAF is linked to elevated catecholamines, oxidative stress, and inflammatory mediators. Dexmedetomidine, a centrally acting alpha-2 agonist with sympatholytic and anti-inflammatory effects, and hydrocortisone, which suppresses inflammatory mediators, may reduce the incidence of POAF.

Methods: A prospective, double-blind randomized controlled trial was conducted on 248 patients undergoing elective on-pump CABG at Ain Shams University Hospital. Patients were randomized into 2 groups: the Treatment Group received dexmedetomidine and hydrocortisone, and the Placebo Group received standard care. The primary endpoint was the occurrence of POAF within 7 days postoperatively.

Results: All 248 patients (124 per group) completed the study. The combined use of dexmedetomidine and hydrocortisone reduced POAF incidence (4.8% vs 12.9%). ICU and hospital length of stay were also shorter in the Treatment Group (2.77 ± 1.12 vs 3.16 ± 1.34 days, P = .012, and 6.63 ± 1.56 vs 7.11 ± 2 days, P = .035, respectively). No differences in hypotension, bradycardia, or wound infections were observed. Hyperglycemia, defined as blood glucose >180 mg/dl, occurred in 8.1% of the Treatment Group and 6.5% of the Placebo Group.

Conclusion: Combining dexmedetomidine and hydrocortisone effectively reduces POAF incidence after CABG, with manageable side effects. Multicenter trials are warranted to confirm these findings.

Excerpts

Postoperative atrial fibrillation (POAF) is the most frequent arrhythmia following coronary artery bypass grafting (CABG), affecting 20%–40% of patients, with a peak incidence within the first 48 h post-surgery

2- to 4-fold increased risk of stroke, a 2-fold increase in all-cause 30-day and 6-month mortality, and a higher likelihood of complications such as the need for a permanent pacemaker, reoperation for bleeding, infection, renal or respiratory failure, cardiac arrest, or cerebral complications

The pathophysiology of POAF is multifactorial, involving inflammation, oxidative stress, and autonomic dysfunction. An inflammatory response characterized by elevated levels of inflammatory mediators, complement activation, leukocyte activation, and C-reactive protein (CRP) complexes is triggered by cardiopulmonary bypass and ischemia/reperfusion insult.

Dexmedetomidine decreases myocardial oxygen demand by reducing heart rate. In addition to its anti-inflammatory qualities, dexmedetomidine decreases sinus and atrioventricular (AV) node activity, making it an important preventive medication for AF following surgery

Steroids may help prevent postoperative AF by modulating the inflammatory process following cardiopulmonary bypass. Studies have demonstrated that preoperative prophylactic corticosteroids reduced the incidence of POAF by approximately 24% in patients undergoing cardiac surgery, including isolated CABG surgery and combined CABG with valve surgery.

While corticosteroids have shown variable success in suppressing inflammation, larger meta-analyses report no significant reduction in POAF incidence and highlight risks like postoperative hyperglycemia

The Treatment Group received a dexmedetomidine infusion initiated at .7 μg/kg/hr IV infusion before aortic cross-clamping.¹² The rate was titrated downward (minimum .2 μg/kg/hr) if systolic blood pressure fell below 90 mmHg or heart rate decreased to <50 bpm...The infusion continued intraoperatively and in the ICU until weaning from mechanical ventilation (mean duration: 12.3 ± 2.1 h). Patients also received hydrocortisone 100 mg intravenous (IV) before aortic cross-clamping and 100 mg every 8 h after surgery, which was continued for 48 h.

Among 248 patients, the Treatment Group receiving dual therapy exhibited a markedly lower POAF rate compared to the Placebo Group (4.8% vs 12.9%), with a relative risk reduction of 62.8% and an absolute risk reduction of 8.1%. Additionally, the intervention was associated with shorter ICU (2.77 ± 1.12 vs 3.16 ± 1.34 days) and hospital stays (6.63 ± 1.56 vs 7.11 ± 2 days).

Adverse effects such as hyperglycemia, hypotension, and wound infections were comparable between groups

Post-cardiac surgery AF is the second most common form of secondary AF and is a unique entity due to special pathophysiological considerations. These mechanisms are not only limited to myocardial ischemia but also include atrial structural disturbances related to venous cannulation during CPB, fluid accumulation in the pericardial sac, pericardial tamponade, the systemic inflammatory response of CPB, autonomic modulation, and anxiety

Citation

Alhadidy MA, Alansary AM, Elghareeb SH. Combined Use of Dexmedetomidine and Hydrocortisone to Prevent New-Onset Atrial Fibrillation After Coronary Artery Bypass Grafting Surgery: A Randomized Clinical Trial. Semin Cardiothorac Vasc Anesth. 2025 Apr 27:10892532251338374. doi: 10.1177/10892532251338374. Epub ahead of print. PMID: 40289414.

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