Clinical trial NCT05674253: Combined Use of Dexmedetomidine and Hydrocortisone to Prevent New Onset AF After CABG Surgery
Official title: Combined Use of Dexmedetomidine and Hydrocortisone to Prevent New Onset Atrial Fibrillation After Coronary Artery Bypass Grafting Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Atrial Fibrillation New Onset
Keywords: Atrial Fibrillation
Coronary artery bypass grafting
Dexmedetomidine
Hydrocortisone
Lead sponsor: Ain Shams University
Sponsor class: OTHER
First posted: 2023-01-06
Enrollment: 248
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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)

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Occurrence of AF
timeFrame: Up to 7 days Postoperative
Secondary outcomes:
measure: ICU stay
timeFrame: Up to 7 days Postoperative
measure: Hospital stay
timeFrame: Up to 10 days Postoperative
measure: Bradycardia
timeFrame: Up to 2 days Postoperative
measure: Hypotension
timeFrame: Up to 2 days Postoperative
measure: Hyperglycemia
timeFrame: Up to 7 days Postoperative
measure: Wound infection
timeFrame: Up to 2 weeks Postoperative
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cardiothoracic Academy, Ain Shams University Hospitals
Study officials:
References:
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