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

NCT ID: NCT05674253

Last Updated: 2023-01-10

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 248 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-25
• Study Completion Date: 2023-07-25

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.

Conditions

Atrial Fibrillation New Onset

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: SINGLE

Study Groups

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 .

Group Type: ACTIVE_COMPARATOR

Dexmedetomidine + Hydrocortisone

Intervention Type: DRUG

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

Standard group

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: DRUG

Other Intervention Names

Medrelaxmidine + Solu-cortef

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Mohamed Alaaeldin Abdelmoneem Alhadidy

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Cardiothoracic Academy, Ain Shams University Hospitals

Cairo, , Egypt

Site Status: RECRUITING

Countries

Egypt

Facility Contacts

University President

Role: primary

gd.research@asu.edu.eg

+2026847819

References

Shen J, Lall S, Zheng V, Buckley P, Damiano RJ Jr, Schuessler RB. The persistent problem of new-onset postoperative atrial fibrillation: a single-institution experience over two decades. J Thorac Cardiovasc Surg. 2011 Feb;141(2):559-70. doi: 10.1016/j.jtcvs.2010.03.011.

Reference Type: BACKGROUND

PMID: 20434173 (View on PubMed)

Greenberg JW, Lancaster TS, Schuessler RB, Melby SJ. Postoperative atrial fibrillation following cardiac surgery: a persistent complication. Eur J Cardiothorac Surg. 2017 Oct 1;52(4):665-672. doi: 10.1093/ejcts/ezx039.

Reference Type: BACKGROUND

PMID: 28369234 (View on PubMed)

Liu C, Wang J, Yiu D, Liu K. The efficacy of glucocorticoids for the prevention of atrial fibrillation, or length of intensive care unite or hospital stay after cardiac surgery: a meta-analysis. Cardiovasc Ther. 2014 Jun;32(3):89-96. doi: 10.1111/1755-5922.12062.

Reference Type: BACKGROUND

PMID: 24495440 (View on PubMed)

Philip I, Berroeta C, Leblanc I. Perioperative challenges of atrial fibrillation. Curr Opin Anaesthesiol. 2014 Jun;27(3):344-52. doi: 10.1097/ACO.0000000000000070.

Reference Type: BACKGROUND

PMID: 24633361 (View on PubMed)

Narisawa A, Nakane M, Kano T, Momose N, Onodera Y, Akimoto R, Kobayashi T, Iwabuchi M, Okada M, Miura Y, Kawamae K. Dexmedetomidine sedation during the nighttime reduced the incidence of postoperative atrial fibrillation in cardiovascular surgery patients after tracheal extubation. J Intensive Care. 2015 May 30;3(1):26. doi: 10.1186/s40560-015-0092-5. eCollection 2015.

Reference Type: BACKGROUND

PMID: 26060574 (View on PubMed)

Keating GM. Dexmedetomidine: A Review of Its Use for Sedation in the Intensive Care Setting. Drugs. 2015 Jul;75(10):1119-30. doi: 10.1007/s40265-015-0419-5.

Reference Type: BACKGROUND

PMID: 26063213 (View on PubMed)

Ueki M, Kawasaki T, Habe K, Hamada K, Kawasaki C, Sata T. The effects of dexmedetomidine on inflammatory mediators after cardiopulmonary bypass. Anaesthesia. 2014 Jul;69(7):693-700. doi: 10.1111/anae.12636. Epub 2014 Apr 28.

Reference Type: BACKGROUND

PMID: 24773263 (View on PubMed)

January CT, Wann LS, Calkins H, Chen LY, Cigarroa JE, Cleveland JC Jr, Ellinor PT, Ezekowitz MD, Field ME, Furie KL, Heidenreich PA, Murray KT, Shea JB, Tracy CM, Yancy CW. 2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol. 2019 Jul 9;74(1):104-132. doi: 10.1016/j.jacc.2019.01.011. Epub 2019 Jan 28. No abstract available.

Reference Type: BACKGROUND

PMID: 30703431 (View on PubMed)

Leung L, Lee LHN, Lee B, Chau A, Wang EHZ. The safety of high-dose dexmedetomidine after cardiac surgery: a historical cohort study. Can J Anaesth. 2022 Mar;69(3):323-332. doi: 10.1007/s12630-021-02167-z. Epub 2021 Dec 29.

Reference Type: BACKGROUND

PMID: 34966972 (View on PubMed)

Al-Shawabkeh Z, Al-Nawaesah K, Anzeh RA, Al-Odwan H, Al-Rawashdeh WA, Altaani H. Use of short-term steroids in the prophylaxis of atrial fibrillation after cardiac surgery. J Saudi Heart Assoc. 2017 Jan;29(1):23-29. doi: 10.1016/j.jsha.2016.03.005. Epub 2016 Apr 7.

Reference Type: BACKGROUND

PMID: 28127215 (View on PubMed)

Church TJ, Haines ST. Treatment Approach to Patients With Severe Insulin Resistance. Clin Diabetes. 2016 Apr;34(2):97-104. doi: 10.2337/diaclin.34.2.97.

Reference Type: BACKGROUND

PMID: 27092020 (View on PubMed)

Engelman DT, Ben Ali W, Williams JB, Perrault LP, Reddy VS, Arora RC, Roselli EE, Khoynezhad A, Gerdisch M, Levy JH, Lobdell K, Fletcher N, Kirsch M, Nelson G, Engelman RM, Gregory AJ, Boyle EM. Guidelines for Perioperative Care in Cardiac Surgery: Enhanced Recovery After Surgery Society Recommendations. JAMA Surg. 2019 Aug 1;154(8):755-766. doi: 10.1001/jamasurg.2019.1153.

Reference Type: BACKGROUND

PMID: 31054241 (View on PubMed)

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. Online ahead of print.

Reference Type: DERIVED

PMID: 40289414 (View on PubMed)

Other Identifiers

FMASU R 261/2022

Identifier Type: -

Identifier Source: org_study_id