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

Sponsor

Ain Shams University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05674253

Collaborator

(none)

248

Enrollment

Location

Arms

Anticipated Duration (Months)

35.6

Patients Per Site Per Month

Study Details

Study Description

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)

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation New Onset	Drug: Dexmedetomidine + Hydrocortisone	Early Phase 1

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

248 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Prevention

Official Title:

Combined Use of Dexmedetomidine and Hydrocortisone to Prevent New Onset Atrial Fibrillation After Coronary Artery Bypass Grafting Surgery

Actual Study Start Date :

Dec 25, 2022

Anticipated Primary Completion Date :

Jun 25, 2023

Anticipated Study Completion Date :

Jul 25, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dexmedetomidine + Hydrocortisone group 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 .	Drug: Dexmedetomidine + Hydrocortisone 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 Other Names: Medrelaxmidine + Solu-cortef
No Intervention: Standard group Patients will not receive dexmedetomidine nor Hydrocortisone and will receive the standard management

Arm

Intervention/Treatment

Active Comparator: Dexmedetomidine + Hydrocortisone group

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 .

Drug: Dexmedetomidine + Hydrocortisone

Other Names:

Medrelaxmidine + Solu-cortef

No Intervention: Standard group

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

Outcome Measures

Primary Outcome Measures

Occurrence of AF [Up to 7 days Postoperative]
The occurrence of an episode of AF postoperatively

Secondary Outcome Measures

ICU stay [Up to 7 days Postoperative]
length of ICU stay in days
Hospital stay [Up to 10 days Postoperative]
length of hospital stay in days
Bradycardia [Up to 2 days Postoperative]
Occurrence of Bradycardia defined as: HR≤50 bpm
Hypotension [Up to 2 days Postoperative]
Occurrence of Hypotension defined as decrease in systolic blood pressure >20%of basal
Hyperglycemia [Up to 7 days Postoperative]
Occurrence of Uncontrolled hyperglycemia Defined as insulin requirement >1 units/kg/day or > 100 units/day of insulin to keep RBS < 180 mg/dL
Wound infection [Up to 2 weeks Postoperative]
The occurrence of Wound infection postoperatively

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.