Combined Use of Dexmedetomidine and Hydrocortisone to Prevent New Onset AF After CABG Surgery

Ain Shams University

Status and phase: Enrolling; Early Phase 1

Conditions: Atrial Fibrillation New Onset

Treatments: Drug: Dexmedetomidine + Hydrocortisone

Study type: Interventional

Funder types: Other

Identifiers

NCT05674253

FMASU R 261/2022

Details and patient eligibility

About

Atrial fibrillation (AF) occurs in 20% to 40% of patients after Coronary artery bypass grafting (CABG) and is associated with numerous detrimental sequelae. In postoperative period, the patient may be exposed to several proarrhythmogenic factors as increased endogenous catecholamines, inflammatory and oxidative mediators secondary to surgical stress and the systemic response to cardiopulmonary bypass, use of inotropic support. Steroids suppress the release of the above-mentioned inflammatory mediators. Dexmedetomidine is sympatholytic, along with anti-inflammatory properties. so combined use of both drugs may have synergistic effect to prevent post operative AF (POAF)

Full description

Postoperative atrial fibrillation (POAF) is a common postoperative complication that occurs in 20% to 40% of patients after Coronary artery bypass grafting (CABAG) and is associated with numerous detrimental sequelae.

POAF is an independent predictor of numerous adverse outcomes, including a 2- to 4-fold increased risk of stroke, reoperation for bleeding, infection, renal or respiratory failure, cardiac arrest, cerebral complications, need for permanent pacemaker placement, and a 2-fold increase in all-cause 30-day and 6-month mortality.

Clinical efforts to prevent and manage POAF following cardiac surgery have thus far presented a major challenge and results have been less than optimal. Despite numerous trials examining prophylactic and treatment modalities, POAF incidence following cardiac surgery has not changed over the past several decades.

The pathogenesis of POAF is incompletely understood but likely involves interplay between pre-existing physiological components and local and systemic inflammation. cardiopulmonary bypass and ischemia/reperfusion injury triggers generalized response characterized by leukocyte and complement activation, high levels of C-reactive protein (CRP) complexes, as well high levels of inflammatory mediators. These mediators, such as interleukins-6 and -8, tumor necrosis factors, leukotriene B4, and tissue plasminogen activator, might contribute to many postoperative complications including atrial fibrillation (AF).

Because of the known physiologic effects of steroids to suppress the release of the above-mentioned inflammatory mediators, steroids might have beneficial effects in decreasing postoperative AF, and inhibiting the inflammatory process post cardiopulmonary bypass. Moreover, they decrease capillary wall permeability, preventing migration of inflammatory mediators into the systemic circulation. Also, Corticosteroids decrease the heterogeneity of atrial conduction and reduce inflammation following cardiac surgery, and studies have shown that preoperative prophylactic corticosteroids reduced POAF incidence without an increased rate of postoperative infection.

Dexmedetomidine is a very specific intravenously and short-acting alpha-2 agonist which theoretically reduces the sympathetic output by decreasing serum levels of norepinephrine and inhibits the release of cytokines and results in reduction of the incidence of tachycardia, inflammation, high blood pressure during and after surgery. Dexmedetomidine reduces heart rate and consequently improves myocardial oxygen demand. It also depresses sinus node and atrial ventricular nodal function which, along with the drug's anti-inflammatory properties, makes dexmedetomidine a reasonable prophylactic drug for postoperative atrial fibrillation.

So, the investigators that combined use of both drugs will have synergistic effect to prevent (POAF) after (CABG) surgery.

Enrollment: 248 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Scheduled for CABG Surgery with cardiopulmonary bypass (CPB) pump

Exclusion criteria

• History of heart block.
• Patients with preoperative bradycardia (HR < 60 / min)
• Patients with preoperative hypotension (systolic blood pressure < 90 mmhg)
• Previous episodes of AF or flutter.
• Uncontrolled diabetes mellitus requiring insulin treatment with recent hyperglycemia which required hospital treatment.
• History of peptic ulcer disease.
• Active systemic bacterial or mycotic infection.
• Permanent pacemaker.
• Any documented or suspected supraventricular or ventricular arrhythmias.
• Urgent or emergency surgery.
• Planned off-pump surgery.
• Patient Refusal.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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248 participants in 2 patient groups

Dexmedetomidine + Hydrocortisone group

Active Comparator group

Description:

Patients will receive dexmedetomidine 0.7 ɥg/kg/hr IV infusion before aortic cross-clamping, and will be continued intra-operatively and in ICU till weaning from mechanical ventilation Patients also will also receive Hydrocortisone 100 mg intravenous (IV) before aortic cross-clamping then 100 mg every 8 hours after surgery which will be continued for 48 hours .

Treatment:

Drug: Dexmedetomidine + Hydrocortisone

Standard group

No Intervention group

Description:

Patients will not receive dexmedetomidine nor Hydrocortisone and will receive the standard management