Desflurane,Brain Natriuretic Peptide and Cardiac Surgery

An Investigation of the Association Between Desflurane Inhalational Agent, Serum Brain Natriuretic Peptide (BNP) Levels and Clinical Outcomes During Coronary Artery Bypass Graft (CABG) Surgery

During coronary artery bypass grafting (CABG) operations with cardiopulmonary bypass (CPB), the use of desflurane continuously or intermittently may have effects on serum brain natriuretic peptide (BNP) levels. The aim is to investigate the association between desflurane, serum BNP values, and clinical outcomes during CABG operations. In a prospective, randomized, double-blinded study, desflurane inhalational anesthesia was administered either continuously or intermittently (Group 1; n=60 versus Group 2; n=62). The preoperative and postoperative BNP levels at 24, 48 and 72 hours after surgery were collected. Outcomes were recorded.

Study Overview

• Status: Completed
• Conditions: Cardiac Surgery; Desflurane; Cardiopulmonary Bypass; Coronary Artery Bypass Graft Surgery; Brain Natriuretic Peptide; Outcome
• Intervention / Treatment: Drug: Desflurane Inhalational agent

Detailed Description

Background: During coronary artery bypass grafting (CABG) operations with cardiopulmonary bypass (CPB), the use of desflurane continuously or intermittently may have effects on serum brain natriuretic peptide (BNP) levels.

Aim of the study: The aim is to investigate the association between desflurane, serum BNP values, and clinical outcomes during CABG operations.

Material and methods: In a prospective, randomized, double-blinded study, desflurane inhalational anesthesia was administered either continuously or intermittently (Group 1; n=60 versus Group 2; n=62). The preoperative and postoperative BNP levels at 24, 48 and 72 hours after surgery were collected. Outcomes were recorded. Randomization into two groups was performed using sealed envelopes. The sequentially numbered assignments of participants were concealed in these envelopes during the study. The patients enrolled in the study receive an allocation to a group after anesthesia induction by health care personnel after the opening of the envelope. The observers were blinded to the anesthetic protocol. Caregivers were not blinded, but they did not participate in data collection or data interpretation. Therefore, the study protocol is considered double-blinded, masked to observers. Inclusion criteria include; 18 to 75 years of age, body mass index of 25 to 31, ejection fraction≥50%. Exclusion criteria include; repeat cardiac surgery, emergent surgery, preoperative coagulation disorder, preoperative congestive heart failure, ejection fraction <49%, preoperative renal dysfunction (serum creatinine>1.3 mg/dL), dialysis, preoperative hepatic dysfunction (serum aspartate/alanine amino transferase>40 U/L), preoperative electrolyte imbalance, history of pancreatitis or current corticosteroid treatment.The primary endpoint was to determine preoperative and postoperative BNP values 24, 48 and 72 hours after surgery. The secondary endpoint was the relation between BNP values and clinical outcomes such as; 1-Aortic cross-clamp time, 2-Cardiopulmonary bypass time, 3-The use of inotropic support, 4-Intra-aortic balloon pump, 5-Duration of mechanical ventilation (>48 hours), 6-Development of pneumonia, 7-Perioperative myocardial infarction, 8-Cerebrovascular event (stroke or transient ischemic attack), seizure, 9-Atrial fibrillation and other rhythm disturbances, 10-Need for renal replacement therapy (RRT), 11-Reoperation secondary to bleeding, 12-Intensive care unit stay (>3 days), 13-Hospital stay and, 14-Thirty-day mortality.

Statistical analysis. The sample size was calculated according to the comparison of serum BNP values in a previous study and a sample size of 58 patients per group would be required with 80% power and the conventional 2-sided type 1 error of 5%. A multiple logistic regression analysis was performed to assess the predictive factors for weaning failure from mechanical ventilation, and the significance level was set at a p-value of less than 0.10 in the univariate model. To determine the best cut-off for preoperative BNP value to predict the development of prolonged mechanical ventilation, we calculated the area under the receiver operating characteristic curve.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Eighteen to seventy-five years of age,
• Body mass index values between twenty-five and thirty-one,
• Ejection fraction greater than or equal to 50%.

Exclusion Criteria:

• Repeat cardiac surgery,
• Emergent surgery,
• Preoperative coagulation disorder,
• Preoperative congestive heart failure,
• Ejection fraction less than 49%,
• Preoperative renal dysfunction (serum creatinine value of greater than 1.3 mg/dL),
• Dialysis,
• Preoperative hepatic dysfunction (serum aspartate/alanine amino transferase values of greater than 40 U/L),
• Preoperative electrolyte imbalance,
• History of pancreatitis,
• Current corticosteroid treatment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Desflurane Continuous; In Group 1 of 60 patients, desflurane inhalational agent was administered continuously during coronary artery bypass graft surgery with cardiopulmonary bypass. Anesthesia induction was administered to all patients with intravenous midazolam at a dose of 0.2 mg/kg, fentanyl at a dose of 5 to 10 µg/kg and rocuronium bromide at a dose of 0.1 mg. For maintenance, in Group 1 patients, desflurane inhalational agent was administered at an end-tidal concentration of 1 to 4% during the whole surgical procedure and intravenous maintenance midazolam at a dose of 0.03 mg/kg and fentanyl at a dose of 1 to 2 µg/kg every half an hour. In Group 1 of patients, during the whole surgical procedure, attention to keep mean arterial pressure above 50 mmHg was provided.	Drug: Desflurane Inhalational agent; Desflurane inhalational agent administration during the whole cardiac surgical operation with cardiopulmonary bypass versus administration of desflurane inhalational agent before and after cardiopulmonary bypass during the whole period of cardiac surgical operation.; Other Names: Suprane
Active Comparator: Desflurane Intermittent; In Group 2 of 60 patients, desflurane inhalational agent was administered intermittently during coronary artery bypass graft surgery with cardiopulmonary bypass. Anesthesia induction was administered to all patients with intravenous midazolam at a dose of 0.2 mg/kg, fentanyl at a dose of 5 to 10 µg/kg and rocuronium bromide at a dose of 0.1 mg/kg. For maintenance, in Group 2 patients, desflurane inhalational agent was administered at an end-tidal concentration of 1 to 4% before and after the cardiopulmonary bypass procedure as intermittently with the addition of intravenous maintenance midazolam at a dose of 0.03 mg/kg and fentanyl at a dose of 1 to 2 µg/kg every half an hour. In Group 2 of patients, during the whole surgical procedure, attention to keep mean arterial pressure above 50 mmHg was provided.	Drug: Desflurane Inhalational agent; Desflurane inhalational agent administration during the whole cardiac surgical operation with cardiopulmonary bypass versus administration of desflurane inhalational agent before and after cardiopulmonary bypass during the whole period of cardiac surgical operation.; Other Names: Suprane

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum BNP values before the cardiac surgery	Serum BNP values were collected from a blood sample of each patient one day before cardiac surgery	One day before cardiac surgery.
Serum BNP values after the cardiac surgery at 24 hours	Serum BNP values were collected from a blood sample of each patient after cardiac surgery	After operation at 24 hours after cardiac surgery.
Serum BNP values after the cardiac surgery at 48 hours	Serum BNP values were collected from a blood sample of each patient after cardiac surgery	After operation at 48 hours after cardiac surgery.
Serum BNP values after the cardiac surgery at 72 hours	Serum BNP values were collected from a blood sample of each patient after cardiac surgery	After operation at 72 hours after cardiac surgery.
Serum BNP values before and after the cardiac surgery	The collected serum BNP values were compared with each other by repeated measure analysis	After collection of the data and during statistical analysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Outcome aortic cross-clamp time	A relation between serum BNP values and aortic cross-clamp time	During operative time period of cardiac surgery
Outcome cardiopulmonary bypass time	A relation between serum BNP values and cardiopulmonary bypass time	During operative time period of cardiac surgery
Outcome use of inotropic support	A relation between serum BNP values and use of inotropic support	During operative time period of cardiac surgery and during intensive care unit stay
Outcome use of Intra-aortic balloon pump	A relation between serum BNP values and use of Intra-aortic balloon pump	During operative time period of cardiac surgery and during intensive care unit stay
Outcome duration of mechanical ventilation (>48 hours)	A relation between serum BNP values and duration of mechanical ventilation (>48 hours)	After operative time period of cardiac surgery and during intensive care unit stay
Outcome development of pneumonia	A relation between serum BNP values and development of pneumonia	After operative time period of cardiac surgery and during intensive care unit stay
Outcome parameters	A relation between serum BNP values and perioperative myocardial infarction	During operative time period of cardiac surgery and during intensive care unit stay
Outcome cerebrovascular event or seizure	A relation between serum BNP values and cerebrovascular event (stroke or transient ischemic attack) or seizure	After operative time period of cardiac surgery and during intensive care unit stay
Outcome atrial rhythm disturbances	A relation between serum BNP values and atrial fibrillation and other atrial rhythm disturbances	After operative time period of cardiac surgery and during intensive care unit stay
Outcome ventricular rhythm disturbances	A relation between serum BNP values and ventricular rhythm disturbances	After operative time period of cardiac surgery and during intensive care unit stay
Outcome renal replacement therapy	A relation between serum BNP values and need for renal replacement therapy (RRT)	After operative time period of cardiac surgery and during intensive care unit stay
Outcome reoperation	A relation between serum BNP values and reoperation secondary to bleeding	After operative time period of cardiac surgery and during intensive care unit stay
Outcome intensive care unit stay	A relation between serum BNP values and intensive care unit stay (>3 days)	After operative time period of cardiac surgery and during intensive care unit stay
Outcome hospital stay	A relation between serum BNP values and intensive care unit stay (>3 days)	After operative time period of cardiac surgery and during intensive care unit stay
Outcome thirty-day mortality	A relation between serum BNP values and thirty-day mortality	After operative time period of cardiac surgery and during intensive care unit stay

Collaborators and Investigators

• Sponsor: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
• Collaborators: Trakya University Faculty of Medicine Hospital
• Investigators: Study Director: Gonul Sagiroglu, MD, Trakya University, Faculty of Medicine, Edirne, Turkey

Publications and helpful links

General Publications

• De Hert SG, Cromheecke S, ten Broecke PW, Mertens E, De Blier IG, Stockman BA, Rodrigus IE, Van der Linden PJ. Effects of propofol, desflurane, and sevoflurane on recovery of myocardial function after coronary surgery in elderly high-risk patients. Anesthesiology. 2003 Aug;99(2):314-23. doi: 10.1097/00000542-200308000-00013.
• Cuthbertson BH, Amiri AR, Croal BL, Rajagopalan S, Alozairi O, Brittenden J, Hillis GS. Utility of B-type natriuretic peptide in predicting perioperative cardiac events in patients undergoing major non-cardiac surgery. Br J Anaesth. 2007 Aug;99(2):170-6. doi: 10.1093/bja/aem158. Epub 2007 Jun 15.
• Karthikeyan G, Moncur RA, Levine O, Heels-Ansdell D, Chan MT, Alonso-Coello P, Yusuf S, Sessler D, Villar JC, Berwanger O, McQueen M, Mathew A, Hill S, Gibson S, Berry C, Yeh HM, Devereaux PJ. Is a pre-operative brain natriuretic peptide or N-terminal pro-B-type natriuretic peptide measurement an independent predictor of adverse cardiovascular outcomes within 30 days of noncardiac surgery? A systematic review and meta-analysis of observational studies. J Am Coll Cardiol. 2009 Oct 20;54(17):1599-606. doi: 10.1016/j.jacc.2009.06.028.
• Uhlig C, Bluth T, Schwarz K, Deckert S, Heinrich L, De Hert S, Landoni G, Serpa Neto A, Schultz MJ, Pelosi P, Schmitt J, Gama de Abreu M. Effects of Volatile Anesthetics on Mortality and Postoperative Pulmonary and Other Complications in Patients Undergoing Surgery: A Systematic Review and Meta-analysis. Anesthesiology. 2016 Jun;124(6):1230-45. doi: 10.1097/ALN.0000000000001120.
• Yun KH, Jeong MH, Oh SK, Choi JH, Rhee SJ, Park EM, Yoo NJ, Kim NH, Ahn YK, Jeong JW. Preoperative plasma N-terminal pro-brain natriuretic peptide concentration and perioperative cardiovascular risk in elderly patients. Circ J. 2008 Feb;72(2):195-9. doi: 10.1253/circj.72.195.
• Fox AA, Nascimben L, Body SC, Collard CD, Mitani AA, Liu KY, Muehlschlegel JD, Shernan SK, Marcantonio ER. Increased perioperative b-type natriuretic peptide associates with heart failure hospitalization or heart failure death after coronary artery bypass graft surgery. Anesthesiology. 2013 Aug;119(2):284-94. doi: 10.1097/ALN.0b013e318299969c.
• Litton E, Ho KM. The use of pre-operative brain natriuretic peptides as a predictor of adverse outcomes after cardiac surgery: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2012 Mar;41(3):525-34. doi: 10.1093/ejcts/ezr007. Epub 2011 Oct 20.
• Hutfless R, Kazanegra R, Madani M, Bhalla MA, Tulua-Tata A, Chen A, Clopton P, James C, Chiu A, Maisel AS. Utility of B-type natriuretic peptide in predicting postoperative complications and outcomes in patients undergoing heart surgery. J Am Coll Cardiol. 2004 May 19;43(10):1873-9. doi: 10.1016/j.jacc.2003.12.048.
• Murad Junior JA, Nakazone MA, Machado Mde N, Godoy MF. Predictors of mortality in cardiac surgery: brain natriuretic peptide type B. Rev Bras Cir Cardiovasc. 2015 Mar-Apr;30(2):182-7. doi: 10.5935/1678-9741.20150008.
• Lurati Buse GA, Koller MT, Burkhart C, Seeberger MD, Filipovic M. The predictive value of preoperative natriuretic peptide concentrations in adults undergoing surgery: a systematic review and meta-analysis. Anesth Analg. 2011 May;112(5):1019-33. doi: 10.1213/ANE.0b013e31820f286f. Epub 2011 Mar 3.
• Cuthbertson BH, Croal BL, Rae D, Gibson PH, McNeilly JD, Jeffrey RR, Smith WC, Prescott GJ, Buchan KG, El-Shafei H, Gibson GA, Hillis GS. N-terminal pro-B-type natriuretic peptide levels and early outcome after cardiac surgery: a prospective cohort study. Br J Anaesth. 2009 Nov;103(5):647-53. doi: 10.1093/bja/aep234. Epub 2009 Aug 27.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2013
• Primary Completion (Actual): August 31, 2014
• Study Completion (Actual): September 30, 2014

Study Registration Dates

• First Submitted: January 13, 2020
• First Submitted That Met QC Criteria: January 20, 2020
• First Posted (Actual): January 23, 2020

Study Record Updates

• Last Update Posted (Actual): January 23, 2020
• Last Update Submitted That Met QC Criteria: January 20, 2020
• Last Verified: January 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics, General; Anesthetics; Anesthetics, Inhalation; Desflurane
• Other Study ID Numbers: 2013.3/13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD sharing plan includes sharing of the Study Protocol, Statistical Analysis Plan, and Statistical Analysis of the study with researchers upon request via e-mail.
• IPD Sharing Time Frame: The Study Protocol, the Clinical Study Report and the Statistical Analysis Plan are available after ClinicalTrials.gov registration.
• IPD Sharing Access Criteria: Accessible to all researchers
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No