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

Atrial Fibrillation New Onset Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05674253
• Other study ID #: FMASU R 261/2022
• Status: Recruiting
• Phase: Early Phase 1
• Start date: December 25, 2022
• Est. completion date: July 25, 2023

Study information

• Verified date: January 2023
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 248
• Est. completion date: July 25, 2023
• Est. primary completion date: June 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Atrial Fibrillation
• Atrial Fibrillation New Onset

Intervention

Drug:
• Dexmedetomidine + Hydrocortisone
Patients will receive dexmedetomidine 0.7 ?g/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

Locations

Country	Name	City	State
Egypt	Cardiothoracic Academy, Ain Shams University Hospitals	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

Country where clinical trial is conducted

Egypt, 

References & Publications (12)

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. — View Citation

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. Erratum In: Clin Diabetes. 2016 Jul;34(3):168. — View Citation

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. — View Citation

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. — View Citation

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. Erratum In: J Am Coll Cardiol. 2019 Jul 30;74(4):599. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Occurrence of AF	The occurrence of an episode of AF postoperatively	Up to 7 days Postoperative
Secondary	ICU stay	length of ICU stay in days	Up to 7 days Postoperative
Secondary	Hospital stay	length of hospital stay in days	Up to 10 days Postoperative
Secondary	Bradycardia	Occurrence of Bradycardia defined as: HR=50 bpm	Up to 2 days Postoperative
Secondary	Hypotension	Occurrence of Hypotension defined as decrease in systolic blood pressure >20%of basal	Up to 2 days Postoperative
Secondary	Hyperglycemia	Occurrence of Uncontrolled hyperglycemia Defined as insulin requirement >1 units/kg/day or > 100 units/day of insulin to keep RBS < 180 mg/dL	Up to 7 days Postoperative
Secondary	Wound infection	The occurrence of Wound infection postoperatively	Up to 2 weeks Postoperative