Clinical trial NCT04238806: Desflurane,Brain Natriuretic Peptide and Cardiac Surgery
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Brain Natriuretic Peptide
Coronary Artery Bypass Graft Surgery
Cardiac Surgery
Cardiopulmonary Bypass
Desflurane
Outcome
Lead sponsor: Kartal Kosuyolu Yuksek Ihtisas Education and Research Hospital
Sponsor class: OTHER_GOV
Collaborators: name: Trakya University Faculty of Medicine Hospital
First posted: 2020-01-23
Enrollment: 151
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serum BNP values before the cardiac surgery
timeFrame: One day before cardiac surgery.
measure: Serum BNP values after the cardiac surgery at 24 hours
timeFrame: After operation at 24 hours after cardiac surgery.
measure: Serum BNP values after the cardiac surgery at 48 hours
timeFrame: After operation at 48 hours after cardiac surgery.
measure: Serum BNP values after the cardiac surgery at 72 hours
timeFrame: After operation at 72 hours after cardiac surgery.
measure: Serum BNP values before and after the cardiac surgery
timeFrame: After collection of the data and during statistical analysis
Secondary outcomes:
measure: Outcome aortic cross-clamp time
timeFrame: During operative time period of cardiac surgery
measure: Outcome cardiopulmonary bypass time
timeFrame: During operative time period of cardiac surgery
measure: Outcome use of inotropic support
timeFrame: During operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome use of Intra-aortic balloon pump
timeFrame: During operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome duration of mechanical ventilation (>48 hours)
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome development of pneumonia
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome parameters
timeFrame: During operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome cerebrovascular event or seizure
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome atrial rhythm disturbances
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome ventricular rhythm disturbances
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome renal replacement therapy
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome reoperation
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome intensive care unit stay
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome hospital stay
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
measure: Outcome thirty-day mortality
timeFrame: After operative time period of cardiac surgery and during intensive care unit stay
Other outcomes:
Locations:
Study officials:
affiliation: Trakya University, Faculty of Medicine, Edirne, Turkey
name: Gonul Sagiroglu, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.