European Journal of Cardiovascular Medicine

Postoperative rhythm disorders are a significant complication following open-heart surgery, with the incidence of supraventricular arrhythmias reported to be between 11% and 54%, and ventricular arrhythmias between 1.8% and 13% (1). These arrhythmias commonly manife st within the first 48 hours after surgery, highlighting the need for diligent postoperative monitoring. A deeper understanding of the factors contributing to the onset and progression of these arrhythmias could lead to a reduction in the need for pharmacological and electrica l interventions to control ventricular rate or restore normal sinus rhythm, thereby decreasing the occurrence of arrhythmias and shortening both ICU and hospital stays.

Although some of these drugs may unintentionally raise myocardial oxygen demand, beta- blockers and negative inotropes are presently the main drugs used to treat postoperative arrhythmias. Despite being a frequently used tactic, there is little data to support the effectiveness of pharmaceutical cardioversion. Furthermore, the research has not directly compared electrical and pharmaceutical cardioversion; yet, the introduction of biphasic electrical cardioversion has demonstrated superiority in attaining sinus rhythm (2). Pharmacological cardioversion's primary disadvantage is the possibility of harmful side effects; its effectiveness is greatest when it is given within seven days of the commencement of recently discovered atrial fibrillation (AF) (3). The effectiveness of pharmaceutical cardioversion is further restricted by persistent AF. Notably, digoxin and sotalol are generally contraindica ted for pharmacological cardioversion of AF (4). Among antiarrhythmic drugs, amiodarone has demonstrated the most promising results, achieving successful conversion and maintenance of normal sinus rhythm in 50-70% of patients (5), with a rapid onset of action when administ ered intravenously (6,7).

Amiodarone is a class III antiarrhythmic drug, widely used in the treatment of refractory arrhythmia especially VT, VF, and wide complex tachycardia. A common recommendation for the management and prevention of any arrhythmias after CPB is intraoperative magnesium. However, some of the disadvantages of magnesium therapy include delayed extubatio n, sedation, hypotension, increased postoperative bleeding, and increased energy requirement for defibrillation. The main goal of this research is to determine how well prophylactic intraoperative single- dose intravenous amiodarone works to restore normal sinus rhythm to atrial fibrillation, whether it can prevent arrhythmias following the release of the aortic cross-clamp, and how long sinus rhythm maintenance lasts in patients having valve replacement surgery.

This prospective observational study was conducted at the U.N.Mehta Institute of Cardiology and Research Center comprising 100 adult patients undergoing Aortic valve replacement during the time period of May 2022 to April 2024 to evaluate the efficacy of Amiodarone and Magnesium Sulphate for Prophylaxis of arrhythmia.

The sample size was calculated using the number of surgeries performed at our institute within the time frame. Raosoft, Inc. software was used with a 95% confidence interval and 5% margin of error. Sample size formula= [z2*σ (1-σ]/e2] z = z-score, e = margin of error,σ = standard deviation.

The study was approved by our institutional ethical committee. Informed written consent was obtained from the patients or relatives of the patients. (EC/Approval/10/C.Anae/13/06/2022)

Inclusion criteria: All patients above 18 years of age or who presented with Aortic stenosis not meeting any of the exclusion criteria included in the study.

Exclusion Criteria: Pregnancy, thyroid disease, heart rate less than 50 beats per minute, NYHA IV, sick sinus rhythm, atrioventricular block, elevated liver enzyme levels, serum creatinine greater than 2 milligrams per deciliter, and use of cimetidine, phenytoin, cholestyramine, or cyclosporine were among the exclusion criteria. Additionally, excluded were those on amiodarone medication or those with amiodarone allergies. Patients were assigned to both groups using a computerized randomizatio n process. During the CPB rewarming interval, patients were split into two groups: Group A (n = 50) received amiodarone, and Group M (n = 50) received magnesium sulfate. The day before surgery, patients were seen during the preoperative phase.

Anesthetic Management:

Anesthesia was administered in accordance with institutional guidelines. Intravenous fentanyl (5µg/kg) and midazolam (0.1 mg/kg) were used to induce anesthesia. Vecuronium (0.1 mg/kg) was used to establish neuromuscular blockade. Vecuronium (0.08 mg/kg), fentanyl (1µg/kg), and sevoflurane at 0.6–0.8 MAC were used to maintain anesthesia. A radial or femoral artery catheter for measuring systemic arterial blood pressure and intermittent arterial blood gas sampling, as well as a triple lumen right internal jugular for central venous pressure monitor ing and the administration of inotropic agents and vasoactive drugs, were used in addition to standard monitoring methods such as five lead electrocardiograms (ECG), pulse oximetr y, temperature monitoring (nasopharyngeal probe), and urine output by Foley's catheterization. Following the intravenous injection of 400 IU/kg unfractionated Heparin and the achieveme nt of an active clotting time of >480 seconds, all patients underwent ascending aortic and two- stage cavo atrial cannulation. Before and during CPB, more heparin boluses were administ ered to keep the activated clotting time within this range. CPB with moderate hypothermia to deep hypothermic cardiac arrest underwent surgery. Depending on the surgeon's preference, either Delnido cardioplegia, St. Thomas cardioplegia, or cold blood cardioplegia (4°C) was employed. During the rewarming phase, after checking CPB blood gas Potassium level at 4-

4.5 meq/lt,

Group A was given amiodarone 5mg/kg.

Group B was given magnesium sulfate 40mg/kg.

Both of the groups were monitored and observed for the total CPB and aortic cross-clamp duration, resumption of spontaneous rhythm, the occurrence of an arrhythmia, use of anti- arrhythmic drugs, inotropic supports, the need for pacemaker usage and need of defibrillat io n. Removal of CPB cannulae, administration of protamine, regular hemostasis, and skin closure till ICU transfer, monitoring is maintained.

Post-operative management:

Patients were shifted and intubated to the ICU. The rate of weaning from mechanic a l ventilation and the point of time of extubation were determined by the patient´s fluid balance and gas exchange, pattern of breathing, and daily radiographic findings. Sedation was prolonged and extubation was not delayed for study reasons. Postoperatively at the ICU patients were being monitored for arrhythmia occurrence, hours to wean from mechanical ventilation, duration of ICU stay, and vasoactive inotropic score.

Statistical analysis:

Statistical analysis was performed using SPSS, Version 26.0 (Chicago, IL, USA). The independent sample t-test was used to compare continuous variables. The chi-square test was used to compare the categorical variable. Data were presented as mean ± SD or proportion as appropriate. The "p" value less than 0.05 was considered to be significant.

In our study, 100 patients were divided into two groups, each group containing 50 patients. Demographic data are shown in Table 1.

Table 1: Demographic data

Table 2: Intraoperative data

The mean CPB time in the amiodarone group was 92.71 and in the magnesium group was

105.92. On analysis, the p-value being 0.073, it was non-significant. The mean cross-clamp time in the amiodarone group was 75.34 and in the magnesium group was 0.3013. On analys is, the p-value being 0.3013, the difference was statistically non-significant shown in Table 2.

Table 3: Postoperative data

The inotropic score was calculated using the vasoactive inotropic score formula. In group A, the mean score was 3.842 and in group M the score was 5.22. On analysis, the p-value being 0.22, it was comparable. The mean hours to wean from ventilator support in the group Amiodarone was 10.03 and in the magnesium group was 19.42. The mean length of ICU stay in hours in group A was 43.08 and in group M was 54.44. On analysis the p-value being <0.001, it was statistically significant shown in Table 3.

Table 4: Postoperative complications

The number of patients in whom resumption of spontaneous rhythm in group A was 44 and in group M was 43. On statistical analysis, the p-value being 1 suggests no difference between the groups other than due to chance. The number of patients where the occurrence of arrhythmia detected in group A was 12 and in group M was 36. The number is high in the magnes ium group. On statistical analysis, the p-value being <0.001, it was statistically significant. Due to complete heart block, usage of a pacemaker in both groups was 7, the p-value being 0.7732, it was comparable. Following weaning off CPB, due to the occurrence of arrhythmia, the usage of a defibrillator in group A was in 10 patients, and group M was 34, which is higher in the magnesium group. On analysis, the p-value being 0.0014, it was statistically significant. During the ICU stay period, the patients were being monitored for arrhythmia occurrence. In group A 6 patients and in group 10 patients arrhythmia was detected. The p-value being 0.4132, was comparable.

Globally, aortic stenosis is receiving a lot of attention. Left ventricular hypertrophy (LVH), a pathophysiologic alteration brought on by increased afterload to the myocardium due to aortic stenosis, is a risk factor for cardiac events that can range from an irregular rise in oxygen demand to arrhythmia and even sudden death. With its associated increased myocardial oxygen demand, ventricular fibrillation (VF) after aortic valve replacement is a common and unpleasant occurrence, particularly if it persists during the rewarming phase after aortic cross-clamp removal. Reperfusion injury, ischemia damage, poor myocardial preservation, inadequate desiring, electrolyte imbalance, and/or unmanaged hypothermia are the most frequent reasons of sustained VF during CPB. (8)

A common treatment for refractory arrhythmias, particularly VT, VF, and broad complex tachycardia, is amiodarone, a class III antiarrhythmic medication. (9,10) And magnesium has a role in the intracellular and transmembrane regulation of particular ion channels and ion transport mechanisms. In our study patients were divided into two groups of 50 patients each. Group A was given amiodarone 5mg/kg and patients in Group B were given magnesium sulfate 40mg/kg in the CPB circuit, during rewarming phase. Intraoperative anesthetic technique and postoperative care were standardized for all the patients as per our institution's protocol.

The demographic profiles of both groups were comparable in age and gender. The mean age of patients in group A was 49.86 ±13.312 and in group M was 48.79±14.587 (p=0.703). There were 30 male and 20 female patients in group A, whereas 35 male and 15 female patients were in group M (p=0.4017) which is not significant. Similar findings are found in Sharma S, et al study age, gender, comorbidities such as diabetes, hypertension, smoking, anesthesia technique, and type of procedure were not significantly related to the development of postoperative AF (P > 0.05). (11)

Intraoperative data

CPB and Cross clamp time:

In our study, the mean CPB time in the amiodarone group was 92.71 minutes and in the magnesium group was 105.92 minutes. The average cross-clamp time in the amiodarone group was 75.34 mts and in the magnesium group, it was 82 minutes. On analysis, it was found that both the groups were comparable in terms of CPB duration and aortic cross-clamp time the p- value being >0.05. However, our study reveals that the duration of both CPB time and ACC times was lower in the amiodarone group than in the magnesium group. Dave S, et al. study confirmed that the CPB time >100 min showed a significant association with the onset of postoperative AF, but the duration of CPB in our patients was less than that and was comparable in both the groups (12) (P = 0.104)

Vaso inotropic score:

In group A, the mean score was 3.842 and in group M the score was 5.22. on analysis, the p- value being 0.22, it was comparable.

Ventilation time and the LOS:

In this study, patients receiving amiodarone prophylaxis demonstrated significantly shorter ventilation times and reduced length of ICU and hospital stay compared to those receiving magnesium therapy. The mean hours to wean from ventilator support in the group Amiodarone was 10.03 hours and in the Magnesium group was 19.42 hours. On analysis the p-value being

<0.001, it was statistically significant. The mean length of ICU stay in group A was 43.08 hrs and in group M was 54.44 hrs p=<0.001. In a study by Treggiari‐Venzi MM et al (13) The length of stay in the ICU was significantly longer in patients receiving amiodarone than in the placebo group. (P<0.05)

Arrhythmia occurrence:

 In group A, the occurrence of arrhythmia detected was 12 patients and in group M it was 36. The number is high in the magnesium group. On statistical analysis, the p-value being <0.001, it was statistically significant. In a study by Turk T et al, similar findings indicated that the incidence of new-onset atrial fibrillation was significantly lower in the amiodarone group. However, the contrast aspect in our study was shown in AVR cases, rather than performing it in CABG cases (14). Similar findings were found in the study done by Roy D., who stated that amiodarone was more effective in preventing recurrences of atrial fibrillation than two widely used antiarrhythmic drugs. (15)

Defibrillator usage:

Following weaning off CPB, due to the occurrence of arrhythmia, the usage of a defibrilla tor in group A was in 10 patients, and group M was 34, which is higher in the magnesium group. On analysis, the p-value being 0.0014, it was statistically significant. In a study by Osman Tiryakioglu, et al , they proved that amiodarone was prophylactica l ly more effective with a P value of 0.015 in controlling arrhythmia than the Mg group. (16) Selvaraj T et al, a study aimed at evaluating the impact of a single intraoperative dose of amiodarone on patients with rheumatic VHD and AF undergoing valve replacement surgery. They concluded, the amiodarone group exhibited a lower requirement for cardioversion/defibrillation (1.5 ± 0.54) compared to the control group (2.26 ± 0.73) (p = 0.014) (17) in contrast, the dose of Amiodarone used in their study was 3mg/kg, in contrast to 5mg/kg used in our study.

Arrhythmia occurrence at ICU:

In the ICU period, 6 patients in group A and 10 patients in group M arrhythmia was detected. The p-value being 0.4132, was comparable.

In a study Sandeep Kumar Kar et al., (18) investigated the effect of prophylactic single- dose intravenous amiodarone in patients undergoing valve replacement surgery. Most patients in Group I (92.86%) maintained sinus rhythm without requiring cardioversion or defibrilla t ion postoperatively (p = 0.002). The study concluded that a single prophylactic intraoperative dose of intravenous amiodarone significantly reduced post-bypass arrhythmias compared to the control group. The distinct feature in our study which contrasts with Anupam et al, was we compared Amiodarone with Magnesium, which favors Amiodarone to be more effective in arrhythmia prevention, rather than a comparison done in the control group.

Limitations:

The limitations of this study are small patient volumes. A larger study would be more relevant in finding actual arrhythmia occurrence in CABG or valvular surgery groups of patients. And lack of proof regarding the reduction in both reperfusion arrhythmias and post-CPB arrhythmias to cardiac morbidity and mortality in these groups of patients

Postoperative rhythm disorders in form of arrhythmias are a significant complication follow ing open cardiac surgery and represent a major source of morbidity & mortality. Recurrence of intraoperative& postoperative arrhythmias, usage of defibrillator, VIS score, occurrence of bundle branch block, usage of pacemaker, time to wean from ventilator& ICU stay were Significantly higher in Magnesium sulphate group. So we conclude that Amidarone was found to be effective in preventing arrhythmia, decreased usage of defibrillator, lower VIS score, reduced time to wean from ventilator & ICU stay in patients undergoing Aortic valve replacement.

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