Abstract

Methods: Thirty patients with II and III ASA enrolled in the study were divided into two groups, each with 15 patients: CABG surgery (Group 1, 13 males, 2 females; mean age 62.2±8.6 years) and CABG + valve replacement surgery (Group 2, 13 males, 2 females; mean age 64.1±10.6 years). Patient data were prospectively collected. Anesthetic induction and endotracheal intubation were performed with 10 μg/kg fentanyl and 0.1-0.2 mg/kg etomidate, and 0.15 mg/kg cisatracurium. Isoflurane 1%, cisatracurium 0.1 mg/kg/hr infusion and 0.15 μg/kg/min fentanyl was used for anesthetic maintenance. Systemic and pulmonary arterial pressures were monitored. NT-proBNP levels and troponin T and CK-MB levels were recorded at pre- and postoperative 4th and 12th hours in both groups.

Results: Demographic and hemodynamic data were not significantly different between the two groups. In both groups, NT-proBNP values increased to peak levels at 24 hours postoperatively, however it was not associated with hemodynamic parameters and inotropic support.

Conclusion: There was no statistical difference between NT-proBNP levels in both groups preoperatively. Postoperative NT-proBNP levels were higher in group 2 (longer cross-clamp, and cardiopulmonary bypass time) at the 4th and 12th hours. However the duration in hospital and in the intensive care unit were longer in group 1 patients with high preoperative NT pro-BNP levels.

Recently, brain natriuretic peptide (BNP) secretion levels due to the increased left ventricle volume and pressure have been used in the early diagnosis and treatment of myocardial damage and cardiac failure after cardiac operations.[3-6]

Investigations with BNP level are focused on the early determination of complications like myocardial infarction and cardiac failure due to the ischemia caused by prolonged cross-clamp time in coronary cardiac operations. Increase in BNP is not only determined in prolonged ischemic time complications but is also true for patients with asymptomatic left ventricle dysfunction and also may be in correlation with the patient’s functional capacity and prognosis.[7-9]

Publications show the value of the correlation between BNP and proBNP levels and the early determination and treatment of the cardiac complications during cardiac surgery in coronary artery patients. They all agree that those complications have often been seen with the myocardial damage in complex surgical patients with prolonged cross-clamp time. But we have not found any study on patients who underwent combined coronary and valve surgery. Our aim was to determinate the correlation of the hemodynamic parameters and the BNP levels correlation in the pre- and postoperative period in these patients.

Methods

All patients were visited the day before the operation and informed consent was asked for. All patients were premedicated with 10 mg diazepam in the evening before the operation. On the morning of the operation, they were sedated with 0.05 mg midazolam in the operating room before monitoring and catheterization. Patients were monitored with five lead ECG, noninvasive blood pressure device, and peripheral oxygen saturation (SpO2) probe.

Patients inhaled 2 lt/min, O2 with nasal canulae and canullated in the antecubital veins with 16 G, radial artery with 20 G and right internal jugular vein with 7.5 F intraducers and pulmonary thermodilution catheter (Edwards Lifesciences 7.5 F, Irvine, CA, USA) for continuous cardiac output monitorization, before anesthetic induction with local anesthesia.

Heart rate (HR), systolic, mean diastolic blood pressures, central venous pressure (CVP), pulmonary venous pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac output (CO), body heat, SpO2, and blood gas measurements were determined before anesthetic induction, at the fifth min of intubation, just before incision time, after sternotomy, before and after cardiopulmonary bypass (CPB), at postoperative 1^st, 4^th, 12^th hours; after extubation, and the 24^th hour.

All patients were ventilated with 100 O2 three minutes before induction and the anesthetic induction was started with 10 µg/kg fentanyl and 0.1-0.2 mg/kg ethomidate and intubated with 0.15 mg/kg cis-atracurium injection. Isoflurane 1%, and cis-atracurium 0.1% mg/kg/hr infusion and fentanyl 0.15 μg/kg/min were used for anesthetic maintenance.

N-terminal (NT) proBNP measurements were done from blood samples taken just before anesthetic induction, and postoperative 4^th and 24^th hours. Troponin T, CK-MB, NT-proBNP tests were done with Roche Elecsys 2010 (Roche Elecsys 2010, Indianapolis, USA) with electro-immunoassay processor.

0.1 µg/kg/min cis-atracurium and 0.15 μg/kg/min fentanyl infusion started after the anesthetic induction. Mechanical ventilation was done with 50% O2 and air.

Starting with 3 mg/kg heparin administration, the activated coagulation time was regulated between 450-600 seconds. After endotracheal intubation cardiopulmonary circulation was started. Operations were done with mild hypothermia (28-32 ºC) and hemodilution (Hct, 25-30%) and the arterial oxygen pressure (AOP) maintained between 50-80 mmHg and the pump flow rate was at minimum 2 lt/m².

After releasing the aortic cross-clamp, patients were ventilated with oxygen. With the completion of the operative procedures, normothermia was obtained and the precise preload regulated with the pump prime before termination of the extracorporeal circulation. To maintain Hct at 30%, blood or crystalloid was infused if required. Medications were restarted. Total pump time, aortic cross-clamp time and operative times were registered.

Patients were transported to the ICU with ventilator support and in monitored status.

Heart rate, arterial blood pressure (ABP), CVP, body heat, SpO2, blood gas measurements, CO measurements of the patients were registered at postoperative 1^st, 4^th, 12^th, and 24^th hours. Extubation time, spending time both in the ICU and at the hospital were also registered.

Statistical analysis
Statistical Package for social sciences (SPSS) for Windows 10.0 statistical package (SPSS Inc., Chicago, Illinois, USA) was used for analyses. Comparisons were done with Student’s t-test and Mann-Whitney U-test. Correlating analysis was done with the Pearson test. A p<0.05 was considered significant. Analysis of variance (ANOVA) was used to test for repeated measurements.

Results

Table 1: Patient demographic and peroperative data

Hemodynamic data
Heart rate: Patients’ HR data are shown in table 2. There was no statistically significant difference between two groups (p>0.05).

Table 2: Hemodynamic changes

Heart rate data in group 1 was significantly higher in all the postoperative measurements than the preoperative period (p<0.05).

Systolic arterial pressure (SAP): Data of SAP are shown in table 2. After sternotomy SAP values were higher in group 1 than group 2 and were found statistically significant (p<0,05).

Central venous pressure (CVP): Central venous pressure data are shown in table 2. Only the post-bypass CVP values were higher in group 2 than group 1 (p<0.05).

Pulmonary arterial pressure (PAP): Pulmonary arterial pressure data are shown in table 2. In group 2 preoperative values and values at the time of anesthetic induction, at the post 5^th min of intubation, at the termination of anesthetic induction, at the pre-incision time, at the pre- and post-bypass period and at the postoperative 1^st hour were significantly higher than group 1.

Pulmonary capillary wedge pressure (PCWP): Data of PACWP are shown in table 2. Preoperative, post induction period and post pump period PCWP values were higher in group 2 than in group 1 and were statistically significant (p<0.05).

Cardiac output (CO): Data are shown on the table 2. Cardiac output values were similar in both groups (p>0.05).

NT-proBNP levels: All the data obtained at the preoperative period and at the postoperative 4^th and 24^th hours levels are shown in figure 1.

Fig 1: N-terminal prohormone brain natriuretic peptide levels.

At the preoperative period NT-proBNP levels of the seven patients (40.6%) were below normal limits (125 pg/ml). In the rest of the patients (59.4%) NT-proBNP levels were higher than normal limits. Preoperative NT-proBNP levels of all the patients of group 2 were higher than 125 pg/ml.

In group 1, postoperative mean NT-proBNP level at the 4^th hour was 1287, 8±239.6 pg/ml and the 24^th hour mean NT-proBNP level was 5736, 0±777.2 pg/ml. Those levels were found to be much higher than preoperative levels and the correlation was positive in statistical analyses (p<0.05), but the rise in postoperative mean levels of both groups was not statistically significant.

In group 1, at the postoperative 24^th hours, there was a statistically negative correlation between EF values and NT-proBNP levels (p<0.05). There was also a statistically significant correlation between cross-clamp time and NT-proBNP levels (p<0.05).

Naturally, cross-clamp time in group 2 was longer than group 1 and the difference between the two groups was statistically significant (p<0.05).

Recently, preoperative PAP values and NT-proBNP values correlations have been published.[10] Our findings showed the same correlations. Using Pearson correlation test, pre- and postoperative 4^th hour PAP and NT-proBNP values correlation was found statistically significant (p<0.05 for group 1 and, p<0.01 for group 2).

There was a statistically significant correlation between preoperative PAP and NT-proBNP levels (p<0.05).

At the postoperative fourth measurements, there was statistically significant correlation only in group 2 (p<0.05).

Troponin T and CK-MB levels: Data are shown in table 3. There was no statistically significant correlation at the preoperative period in troponin T levels between two groups (p>0.05). At the postoperative period, troponin T levels were much higher in group 2 and was statistically significant (p<0,05).

Table 3: Troponin T and CK-MB levels

Morbidity and mortality: During the ICU period, one patient in group 2 had an attack of ventricular fibrillation on the second postoperative day. One patient in group 1 who needed intra aortic balloon support during the postoperative period was rehospitalized on the 8^th day after discharge due to pleural effusion. One patient in group 2 was rehospitalized on the 7^th day after discharge due to atrial fibrillation with rapid ventricular response. There was statistically significant correlation between hospital stay and NT-proBNP levels (p<0.05).

Two patients who underwent CABG + aortic valve replacement (AVR) in group 2 died. One patient in group 1 died due to gastrointestinal complication.

Table 4: Patient hospital stay, ICU time and mortality

Discussion

Diminished left ventricular compliance and contractile dysfunction due to myocardial ischemia causes rises in left ventricular end-diastolic and atrial pressures and results in secretion of the natriuretic peptides during CABG surgery.[5-8,11]

In the case of chronic mitral regurgitation and aortic stenosis myocardial decompensation results from different mechanisms and in both conditions it results in ventricular failure. It is known that the more stenotic a valve, the greater the rise of the BNP level.[4]

Brain natriuretic peptide secretion as a response of ventricular wall stretch, secreted from cardiac ventricles is a good parameter for demonstration of cardiac overload. Secreted BNP from stretched myocardium will be derived in NT-proBNP and BNP structures in the circulating blood.

The active and more effective format is BNP. Since eradication of the BNP from circulating blood is more rapid, it is safer to measure the NT-proBNP level. Also the half life and constant secretion of the NT-proBNP make it a preferred parameter for many centers.

Some investigations are focused on the correlation between valvular disease like aortic stenosis and mitral regurgitation and the BNP or NT-proBNP levels. The result is that the concentration of the plasma BNP is a noninvasive parameter for evaluation of disease progress and the prognosis of the ventricular function loss.[12]

Berendes et al.[6] investigated BNP concentrations in patients receiving CABG, aortic valve, and mitral valve operations. Brain natriuretic peptide concentrations in the preoperative period in patients with valve operations were within normal limits, but the concentration was found high in CABG patients. They showed direct correlations between prolonged cross-clamp time and higher BNP concentration and also the effect of higher preoperative BNP concentrations on higher postoperative mortality. They declared that depending on cross-clamp time, myocardial ischemia and prolonged left ventricular higher pressure and preload results with higher BNP secretion may be a remark for patients with preoperative high BNP concentrations in the postoperative early period.[7]

Like Berendes et al.[6] we also found high NT-proBNP concentrations in patients who underwent concomitant CABG and valve replacement (Group 2), due to the longer cross-clamp time. But the difference was not statistically significant between two groups (p>0.05). The highest BNP concentration was found at the 24th hour measurement in a patient who underwent CPB twice in group 2.

Weber et al.[4] demonstrated that high NT-proBNP concentrations in aortic valve disease correlated with the severity of the pathology and NT-proBNP concentration falls with the surgical treatment of the disease. In patients who were treated conservatively, the NT-proBNP concentrations were higher as the disease progressed. They stated that in evaluating the myocardial stress and monitoring the aortic valve disease prognosis NT-proBNP concentrations may be used as a biochemical marker.

We found higher BNP concentrations preoperatively in group 2. The ICU stay and hospitalization of the patients were longer and mortality rate was higher in this group although there was no statistically significant difference. Despite the small number of patients, we observed that preoperative elevated BNP concentrations may be a higher risk factor for cardiac surgery.

Saribulbul et al.[14] demonstrated in their study that there were significant correlations between preoperative BNP concentrations, cross-clamp time and the use of inotropics. They found higher cross-clamp time in patients with preoperative high BNP levels.

The highest BNP concentration was found at the 24^th hour and sustains seven days postoperatively.[5,6] In group 2 who underwent concomitant operations, two patients underwent mitral valve replacement and 13 patients underwent AVR. NT-proBNP levels in both groups were higher in group 2; however it was not statistically significant (p>0.05).

Although there was no significant difference in hospital stay and ICU in groups 1 and 2, ICU stay was a bit longer in group 2.

NT-proBNP concentrations may be used preoperatively as a risk factor parameter and may be a monitoring marker at the postoperative early period and also a prognostic indicator in cardiac surgery.

Declaration of conflicting interests
The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Funding
The study was funded by the Medical Research Fund of Akdeniz University.

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