COMPARISON BETWEEN THE EFFECT OF AMIODARONE AND LIDOCAINE WITH MAGNESIUM SULFATE ON OCCURRENCE OF REPERFUSION VENTRICULAR FIBRILLATION AFTER AORTIC CROSS CLAMP RELEASE ON AORTIC VALVE SURGERY.

Background :Reperfusion ventricular fibrillation (VF) after aortic cross-clamp (ACC) release is one of the most common complications after Aortic valve surgery. normal by a 3 release. protocol cardiopulmonary were the General anesthesia was induced with fentanyl 5µg/kg, midazolam 0.1-0.2 mg/kg, and atracurium 0.5 mg/kg, and anesthesia was maintained using fentanyl 2 µg/kg before sternal incision, isoflurane 1 vol %, and atracurium 5 µg/kg/min. The operation was performed through a standard median sternotomy with cardiopulmonary bypass (CPB) (Sorin C5) machine with a flow rate of 2.4-4.2 l/m 2 and moderate hypothermia at 30°C. CPB was instituted with a standard kit and a hollow-fiber membrane oxygenator (Sorin). The CPB circuit was primed with Ringer’s acetate and carefully de-aired. Standard cannulation consisted of arterial cannulation in the distal part of the ascending aorta and a 2-stage venous cannula inserted into the right atrium and the inferior vena cava. Myocardial preservation consisted of either anterograde or intermittent antegrade and retrograde cardioplegia. Cardioplegia was repeated every 20 to 30 minutes or on the return of electrical activity of the heart. normal way of minutes before aortic cross clamp


ISSN: 2320-5407
Int. J. Adv. Res. 7(4), 1128-1133 1129 Numerous mechanisms have been suggested to give an explanation for the elevated incidence of VF, as well as ischemia-mediated increases in reentry, automaticity, and reperfusion injury. (Kaplinsky et al., 1981) VF may lead to greater than before myocardial oxygen consumption, enlargement of the ventricle with consequential wall tension increase, and myocardial tissue acidosis. (Lockerman et al., 1987) These changes may be especially obvious within the hypertrophied ventricle when the mean arterial blood pressure is lower than 50 to 60 mm hg. (Spadaro et al., 1982) Despite the fact that VF is thought to adversely have an effect on the heart, the ''gold standard'' management is internal direct-current shock, which could be harmful. animal models using monophasic damped sine waveform shocks suggest that defibrillation leads to diminished myocardial performance and microscopic damage to myocytes as well as the injury is more obvious with frequent shocks with a short time between shocks. (Yamaguchi et al.,

2002)
From these data, the prevention of reperfusion VF or a reduction in the defibrillation attempts needed to discontinue VF could be of advantage in saving myocardial function after cardiopulmonary bypass (CPB). lidocaine, a class IB (Na channel blocking) anti-arrhythmic medication, has a long history of use in cardiac surgical procedure for the prophylaxis of VF. many studies have demonstrated that its effectiveness in preventing VF and reducing the shocks needed to defibrillate VF. The goal of the present study was to evaluate whether amiodarone or lidocaine with magnesium sulfate was superior to placebo for the prevention of VF after aortic cross clamp removal in patients undergoing aortic valve surgery.

Materials And Methods:-
This randomized controlled trial study was conducted in Beni Suef university Hospital from 2/2016 to 2/2018 after approval by the internal ethical committee. Written informed consent was taken from all patients before the start.
Patients were eligible for inclusion if they were undergoing an elective aortic valve procedure that was expected to include cross clamping of the aorta. Patients excluded from the study who had history of treatment with digoxin, amiodarone, or lidocaine (including cardiopulmonary resuscitation). Also, patients had Contraindications to amiodarone (sick sinus syndrome, atrioventricular conduction abnormalities, thyroid disease, interstitial lung disorders, renal or liver disease, and known allergic or toxic reactions to amiodarone) or patients with Combined cardiac surgery and emergent operation.
Patients were randomly assigned to three groups in a 1:1:1 fashion. Group A received 300 mg of amiodarone diluted with normal saline to 25ml, group B received 5ml of lidocaine 2% (100 mg) and 2g magnesium sulfate (25ml), and group C (control group) received 25 ml normal saline by the way of pump circuit, 3 minutes before aortic cross clamp release. All study drugs were prepared by a research pharmacist and diluted to 25 mL total volume. Anesthesiologists, surgeons, and CPB perfusionists were strictly blinded as to the content of the syringes.

Procedure
Patients' baseline characteristics will include age, sex, weight and the patients' echocardiographic information included concomitant valve disease and left ventricular ejection fraction (LVEF). Standard clinical protocol was used for all patients. Complete blood count, a standard coagulation profile and electrolytes was performed a day before surgery.
The operation was performed through a standard median sternotomy with cardiopulmonary bypass (CPB) (Sorin C5) machine with a flow rate of 2.4-4.2 l/m 2 and moderate hypothermia at 30°C. CPB was instituted with a standard kit and a hollow-fiber membrane oxygenator (Sorin). The CPB circuit was primed with Ringer's acetate and carefully de-aired. Standard cannulation consisted of arterial cannulation in the distal part of the ascending aorta and a 2-stage venous cannula inserted into the right atrium and the inferior vena cava. Myocardial preservation consisted of either anterograde or intermittent antegrade and retrograde cardioplegia. Cardioplegia was repeated every 20 to 30 minutes or on the return of electrical activity of the heart.
Patients were randomly assigned to three groups. Group A received 300 mg of amiodarone diluted with normal saline to 25 ml, group B received 25 ml of lidocaine 2% (100 mg) and 2 g magnesium sulfate (25 ml), and group C (control group) received 25 ml normal saline by the way of pump circuit, 3 minutes before aortic cross clamp release.
Intraoperative variables included ACC time, CPB time, cardioplegic volume, and two samples for electrolyte and arterial blood gas (ABG) values. Patients weaned from CPB when rewarmed to core temperature of at least 37°C and were hemodynamically stable. Electrolyte and ABG values tested once more after weaning from CPB. Whenever the patient's rhythm will be VF after ACC release, the antiarrhythmic drug was reused and the patient was treated with internal biphasic truncated exponential direct current (DC) shock with stepwise increasing energy at the frequency of 20 J. Furthermore, in spite of normal ABG and serum level of electrolytes, if this did not lead to a stable rhythm, a 30-J shock was given after the administration of another dose of antiarrhythmic drug. Reuse of antiarrhythmic drug means another single dose of lidocaine in group A, amiodarone in group B, and lidocaine and magnesium sulfate in group C. It should be mentioned that surgeons were blinded to the type of drugs during this study.

Outcome Measurements
Patient demographics were recorded and included age, gender, weight, left ventricular ejection fraction, duration of CPB, duration of aortic cross clamping, volume of cardioplegia and duration of operation. The primary outcomes were compared among the 3 study groups including the incidence of VF after aortic cross clamp removal and the second outcomes were the number of defibrillations required to terminate VF.

Sample Size
In this study there were three independent groups, the significance of the differences in three sample means is being evaluated using F-test (ANOVA). The alpha level is α=0.05, effect size =0.39 and the power is 0.90. Using G Power, for the total sample size at f=3.1 and degree of freedom=2 was 87 patients in the three groups.

Statistical Methods
Data were collected, entered and analyzed by IBM SPSS version 22 for windows. Categorical variables were analyzed using chi-square tests or Fisher exact test (where appropriate), whereas continuous variables were compared using analysis of variance or Kruskal-Wallis tests (where appropriate regarding normality tests). All statistical tests were 2-sided with the alpha level set at 0.05 for statistical significance. P-value was considered significant at less than 0.05).

Results:-
A total of 87 patients were enrolled in the trial. There were 29 patients in group A, 29 patients in group L, and 29 patients in group P. Base line characteristics of patients under the study were summarized in table (1), bypass criteria in table (2), Impact of using the lidocaine, amiodarone and saline on arrhythmia and need of DC shock in table (3) and troponin level after 24 hours in figure (1). Data of Age, weight and ejection fraction presented as mean and standard deviation(SD) and of gender and main valve lesion as number and percentage

Discussion:-
In this trial of patients undergoing aortic valve procedures, neither amiodarone nor lidocaine given 3 minutes before aortic cross clamp removal decreased the incidence of VF. However, amiodarone, but not lidocaine, decreased the number of shocks required to terminate VF.
Many studies have shown lidocaine to decrease the reperfusion VF incidence when compared with control groups. In a large trial, Ayoub and colleagues randomized 120 patients undergoing CABG to receive 150 mg amiodarone, 100 mg lidocaine, or placebo 2 minutes before removal of the aortic cross clamp. They found that VF incidence was higher in the groups receiving amiodarone or placebo versus the group receiving lidocaine (48% vs. 45% vs. 20% respectively, P = 0.031). However, they found the energy required to terminate VF was lower in the patients receiving amiodarone versus the controls (16 ± 7 J vs. 25 ± 8 J; P= .023). (Ayoub et al., 2009) The dose of amiodarone used in this study was significantly higher than the dose used in the two previous investigations 300 mg vs 150 mg. This dose was selected according to the large volume of distribution of amiodarone and the expected hemodilution in the CPB reservoir. Even with this larger dose, it was unable to replicate the decrease in VF found by Samantaray and colleagues. (Samantaray et al., 2010) Our results were similar to those of Ayoub and colleagues, who found no difference in the incidence of VF, but that VF was more easily terminated in patients receiving amiodarone. 29 patients who were taking amiodarone preoperatively had a decreased incidence of VF but not statistically significant and required fewer shocks to terminate VF but they suggest that an intravenous bolus of 300 mg of amiodarone may not be adequate to achieve therapeutic tissue levels in the myocardium. Future studies aimed at preventing reperfusion VF may focus on preoperative loading of patients with oral amiodarone.

Troponin level after 24 hours
Troponin level after 24 hours