Desflurane,Brain Natriuretic Peptide and Cardiac Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Outcome, Brain Natriuretic Peptide, Coronary Artery Bypass Graft Surgery, Cardiac Surgery, Cardiopulmonary Bypass, Desflurane

Intervention / Treatment
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* Drug: Desflurane Inhalational agent


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Desflurane Continuous<br>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<br>* 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.<br>* Other names: Suprane;|
| Active Comparator: Desflurane Intermittent<br>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<br>* 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.<br>* Other names: Suprane;|

What is the study measuring?
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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 |