|Year : 2015 | Volume
| Issue : 2 | Page : 115-119
Effect of preoperative propranolol on postoperative junctional ectopic tachycardia after complete surgical repair of Tetralogy of Fallot: A prospective observational study
Shankar Vithalrao Kadam, Kamlesh Tailor, Snehal Kulkarni, Smrutiranjan Mohanty, Hari Bipin Radhakrishnan, Suresh G Rao
Department of Congenital Heart Diseases, Congenital Heart Centre, Kokilaben Dhirubahi Ambani Hospital, Mumbai, Maharashtra, India
|Date of Web Publication||30-Jul-2015|
Shankar Vithalrao Kadam
Department of Congenital Heart Diseases, Kokilaben Dhirubhai Ambani Hospital, Four Bungalows, Andheri (West), Mumbai - 400 053, Maharashtra
Source of Support: None, Conflict of Interest: None
Background: Postoperative junctional ectopic tachycardia (JET) is a common and transient phenomenon occurring after repair of Tetalogy of Fallot (TOF). Although propranolol is used in these patients to prevent and control hypercyanotic spells, its effects are not widely studied in postoperative scenario.
Aims: The aim of this study was to examine the effect of preoperative use of propranolol on the incidence of postoperative JET after complete surgical correction of TOF.
Materials and Methods: This is a prospective observational study of 51 patients undergoing complete repair of TOF between July 2010 and February 2012. Of these, 25 patients did not receive propranolol (control group) and 26 patients did receive it (propranolol group).
Results: Lowest hematocrit on Cardiopulmonary Bypass (CPB) was significantly low in control group compared to propranolol group (P = 0.008). Though inotropic score was high (P = 0.015), incidence of postoperative JET was significantly low in propranolol group compared to control group (P = 0.040).
Conclusions: Our findings suggest that the preoperative use of propranolol is associated with a lower incidence of JET after complete surgical repair of TOF. A randomized control trial should be considered to explore causality.
Keywords: Junctional ectopic tachycardia, propranolol, tetralogy of Fallot
|How to cite this article:|
Kadam SV, Tailor K, Kulkarni S, Mohanty S, Radhakrishnan HB, Rao SG. Effect of preoperative propranolol on postoperative junctional ectopic tachycardia after complete surgical repair of Tetralogy of Fallot: A prospective observational study. Nig J Cardiol 2015;12:115-9
|How to cite this URL:|
Kadam SV, Tailor K, Kulkarni S, Mohanty S, Radhakrishnan HB, Rao SG. Effect of preoperative propranolol on postoperative junctional ectopic tachycardia after complete surgical repair of Tetralogy of Fallot: A prospective observational study. Nig J Cardiol [serial online] 2015 [cited 2019 Nov 20];12:115-9. Available from: http://www.nigjcardiol.org/text.asp?2015/12/2/115/152010
| Introduction|| |
Junctional ectopic tachycardia (JET) is frequently reported after surgical repair of Tetralogy of Fallot (TOF). ,, Various studies have shown that operations for congenital heart diseases like ventricular septal defect closure, TOF repair, complete atrioventricular canal repair, and the Fontan operation are major contributors of postoperative JET. ,,,,, Repair of TOF involves closure of ventricular septal defect and relief of right ventricular outflow tract obstruction (RVOTO). Low operative weight, cardiopulmonary bypass time >100 minutes, immediate postoperative serum lactic acid levels >20 mg/dl are some of the risk factors other than TOF. ,, The causes of JET are multifactorial after repair of TOF. Increased excitability of conduction tissues is the cause, probably due to irritation and surgical trauma during Ventricular septal defect (VSD) closure and ventriculotomy.  Patients with JET have higher requirement of noradrenaline, longer ventilation time, intensive care unit (ICU), and hospital stay. ,, A variety of therapeutic strategies has been reported to control JET that include the use of beta-blockers, moderate cooling of the patients to maintain core temperature of ~35°C, amiodarone, and recently, use of dexmeditomedine. ,,,
Propranolol is a frequent medication used in patients with TOF to control hypercyanotic spells. , The effectiveness of propranolol is due to its property of reduction in right ventricular (RV) outflow impedance.  There is little information regarding the relation between preoperative use of propranolol and its effect on postoperative incidence of JET.
We undertook this study to evaluate the effect of preoperative use of propranolol on the incidence of postoperative JET in patients after complete surgical repair of TOF.
| Materials and methods|| |
Study was initiated after obtaining permission from institutional ethics committee. Informed parent consent was taken for use of propranolol and later for surgical repair of TOF. Patient with history of cyanotic spells and excessive cry were put on propranolol at 1 mg/kg/day in two divided doses at about 4 months of age. Those without this history were followed regularly till surgery. This is a prospective observational study on 51 consecutive patients undergoing corrective surgical repair of TOF at our institution between July 2010 and December 2011. Patients who underwent initial palliative shunt were excluded from the study. Data collection was done in the operation theater and pediatric cardiac ICU in the postoperative period. If JET was suspected on monitor, it was confirmed with standard 12 lead electrocardiogram (ECG) and atrial wire ECG. There were 51 patients who met our inclusion criteria. Two patients groups were identified: The propranolol group (n = 26), who received propranolol preoperatively and the control group, who did not receive propranolol preoperatively coming for complete surgical correction (n = 25). Patients with reactive airway disease, in congestive cardiac failure and with aortic regurgitation were not started on propranolol. Last dose was administered on the day of surgery. Average duration of propranolol use was 14 months before surgery. Hematocrit and heart rate were monitored in these patients with TOF.
Anesthesia, CPB, and surgical management
After premedicating with Inj. Glycopyrrolate 10 mcg/kg and Inj. Ketamine 2 mg/kg intravenous (IV) stat in the preoperative waiting area, baby was shifted in the operating room. Endotracheal intubation was done after giving Inj. Fentanyl and Inj. Vecuronium. Arterial blood pressure (ABP) was monitored with a radial arterial line and central venous pressure (CVP) through the internal jugular vein (IJV). Surgery was conducted using similar techniques by same team of surgeons, anesthesiologist, and perfusionist during the study period under standard cardiopulmonary bypass (CPB) techniques. RVOT repair was done according to level and severity of obstruction across RVOT. Though pulmonary valve preserving procedures like RV outflow patch and infundibular resection was preferred, patient's anatomy compelled us to put a transannular patch across pulmonary annulus or a right ventricle to pulmonary artery conduit in many patients. Cardiac arrest was achieved with modified Del Nido cardiplegia in all patients. Before coming off CPB we have given, 30 mg/kg of magnesium was given in the CPB circuit. Weaning off CPB was done with moderate inotropic support of Inj. adrenaline 0.04 mcg/kg/min and Inj. Milrinone 0.5 mcg/kg/min in all cases.
Standard 12-lead ECGs were taken in all patients preoperatively and in the ICU after surgery, once patient was stabilized. We monitored patients with Drager monitors. ECG, arterial blood pressure (ABP), central venous pressure (CVP), end tidal carbon dioxide (EtCO2), saturation of pulsatile tissue (SpO2), and urine output (UO) were monitored in all patients. Left atrial pressure (LAP) monitoring was done in few hemodynamically unstable patients using direct LAP line. Continuous monitoring of all above parameters was done during initial ICU stay.
Diagnostic criteria for JET included the following: 1) Tachycardia with QRS similar to sinus rhythm QRS, 2) a ventricular rate more than 170 beats/min, 3) atrioventricular dissociation with or without hemodynamic compromise, and 4) a ventricular rate faster than the atrial rate. 
When JET was suspected on the monitor, it was confirmed with a standard 12 lead ECG and atrial-wire ECG whenever diagnosis is not clear.
Same intensive monitoring was continued for 48 hrs post extubation, or JET-free period, or off inotrope without any incidence of low cardiac output.
Management of postoperative JET
After diagnosis of JET, our treatment protocol was initiated immediately in hemodynamically unstable patients. Goal of the treatment was to convert JET into a stable rhythm. JET diagnosis was done with 12 lead ECG. Atrial-wire ECG was done when diagnosis was not confirmed on 12 lead ECG. Then optimization of sedation and analgesia was considered. Dexmeditomedine infusion was started for its sedative, mild analgesic, and rate control properties. Fentanyl boluses were given in addition to dexmeditomedine infusion whenever required. Then we optimized inotropic support, i. e., we tried to reduce adrenaline infusion. This was followed with maintenance dose of digoxin, moderate surface cooling to a core temperature of ~35°C, muscle paralysis with vecuronium, and finally an antiarrhythmic, i.e. amiodarone. Amiodarone was started as 5mg/kg loading dose over 4 hrs followed by 10 mcg/kg/min infusion.
Postoperative intensive care data
Postoperative JET was recorded on monitor and it is confirmed with 12 lead ECG and atrial-wire ECG for patient with unclear diagnosis on 12 lead ECG. Six patients (33%) required atrial wire study for confirmation of diagnosis. Maximum inotrope score was recorded either in immediate post cardio-pulmonary bypass period or during ICU stay.
It is calculated as, Inotropic score = (Dopamine × 1) + (Dobutamine × 1) + (Adrenaline × 100) + (Noradrenaline × 100) + (Milrinone × 10). Dosages in mcg/kg/min.
Statistical analysis was performed with GraphPad statistical program. Data were presented as mean standard deviation (SD) or median with ranges or percentages as appropriate. The Fisher exact, independent sample t-test was used to draw comparisons between propranolol group and the control group. Statistical analysis was performed to find any correlation between the preoperative use of propranolol and the occurrence of postoperative JET using x2-test. Differences were considered to be statistically significant when P - value was ≤ 0.05.
| Results|| |
The preoperative patients' data is shown in [Table 1].
Preoperative oxygen saturation was low in propranolol group compared to control group which was statistically significant. Preoperative heart rate was quite low in propranolol group compared to control group but was not statistically significant. Hematocrit was 46 ± 10 in propranolol group compared to 43.5 ± 7.3 gm% in control group, this difference was not significant. Incidence of cyanotic spells was high in propranolol group compared to control group but was not statistically significant again.
Operative data is summarized in [Table 2] and shows statistically significant differences between two groups with regards to lowest hematocrit on CPB (P value 0.008), hematocrit during coming off CPB (P value 0.001), JET incidence in first 24 hrs after surgery (P value 0.040) and inotrope score in immediate postoperative period (P value 0.015). CPB time was more in propranolol group than control group but it was statistically not significant. Hematocrit recorded on CPB and while coming off CPB was significantly high in propranolol group compared to control group (P value 0.008 and 0.001). Overall incidence of JET in our study was 35.3%. It was documented in 18 patients out of 51 patients in first 24 hrs after surgery. The incidence of postoperative JET was 19.3% in the propranolol group and 52% in the control group. The difference was statistically significant with a P value of 0.04. Inotrope score was high in propranolol group and was statistically significant. So propranolol group required more inotropic support with inotrope score of 17.5 ± 5.5 vs. 13.9 ± 52 for the control group. This difference between the two groups was statistically significant with a P value of 0.015.
Postoperative morbidity and mortality is shown in [Table 3]. One patient in the propranolol group developed complete heart block and there was one mortality on the second postoperative day from severe bi-ventricular dysfunction. There was no significant difference in postoperative wound infection rate and other morbidity indicators. But, if we consider all the issues collectively in two groups, there is increased risk of complications in propranolol group which is statistically significant (P value 0.013).
| Discussion|| |
Propranolol is a non-selective beta-adrenergic receptor blocking agent which is also used in the management of JET. It relives spasm of infundibular muscle of RVOT. This property of propranolol helps in prevention and treatment of TET spells. The mechanism of the anti-arrhythmic effect of propranolol has not been established well. However, it may inhibit pacemaker potentials and decreases frequency of spontaneous depolarization,  thus reducing incidence of JET. Propranolol pharmacokinetic studies have reported biological half-life between 3.2 hrs and 5.2 hrs. , However, the pharmacokinetics of propranolol may be altered by hypothermic cardiopulmonary bypass. Plachetka et al.,  reported that the plasma levels of propranolol decreased with the onset of CPB and there was sustained increase in plasma levels after CPB. This increased plasma level post CPB can have a protective effect over the incidence of JET. Hence, it can be conceived that preoperative use of propranolol has preventive role on postoperative JET.
Incidence of JET after congenital heart surgery in the current era is still high and it is highest after the Rastelli operation. ,,, Surgical procedures involving VSD closure have increased incidence of JET.  In our study, incidence of JET is comparatively higher (35%). This high incidence of JET can be attributed to long CPB time (189 ± 65 min), long AXC time (119.8 ± 42), use of adrenaline, and high inotrope score in both groups. Incidence of JET was low in the propranolol group compared to control group though CPB time (189 ± 65 minutes) and AXC time (119.8 ± 42) were long in that group. Hematocrit on CPB in the propranolol group was high (46 ± 10) compared to the control group (24 + 1.3) which may have a role in prevention of JET. In spite of high inotrope score in propranolol group (17 ± 5.5) compared to control group (13.9 ± 5.2), incidence of JET was lower (19.3%) than control group.
The effect of heparin administration on plasma protein binding is also of importance. Heparin administration results in lipoprotein lipase and hepatic lipase release, which in turn hydrolyze plasma triglycerides into non-esterified fatty acids which can lead to displacement of plasma protein-bound drugs such as propranolol and raises their concentrations.  Lung isolation from the circulation during CPB can cause sequestration of several drugs including propranolol, which may return back to circulation after re-establishment of the pulmonary circulation.  From the pharmacokinetic data of propranolol, we can assume that in the propranolol group due to the effect of hypothermic cardiopulmonary bypass, heparin administration, and lung sequestration might result in therapeutic serum level of propranolol in postoperative period. This therapeutic level of propranolol might have been responsible for decreased incidence on postoperative JET. Another important observation from our study is that the propranolol group required higher doses of inotrope than the control group which was statistically significant. This may be due to the myocardial depression effect of propranolol. Staged treatment protocol is adopted by many centres as the most effective to way to control JET. Dexmeditomedine infusion perioperatively reduces incidence of JET.  Currently, some studies single out amiodarone as having the highest response rate. , It is credited with the most rapid control of the heart rate in post-operative JET.  Beta blockers like esmolol and sotalol have also been used effectively for treatment of JET.  Magnesium supplementation in pediatric patients undergoing surgery for congenital heart defects has been known to have a protective effect from the complication of JET. Magnesium sulphate supplementation after cessation of CPB may eliminate the occurrence of JET on admission into the intensive care unit. ,
Prevention of JET can have a impact on the postoperative course of the patients with reduced duration of mechanical ventilation; ICU stay and total hospital stay; and, in turn, reduction of cost of treatment. ,,
In conclusion, our findings suggest that in spite of high inotropic score, preoperative use of propranolol decreases the incidence of JET after surgical repair of TOF. But overall risk of complications might be more in propranolol group which warrants randomized controlled trial involving more patients.
This study could not be randomized. We have not taken into consideration duration and dosage of preoperative use of propranolol in this study which is important. This study included a relatively small number of patients. We have not studied duration of JET in two groups which may be different with use of propranolol. We have not studied effects of JET on ventilation time, ICU and hospital stay, which could have given more insights in to its overall effects on morbidity. In preoperative demographics and echocardiographic data, size of pulmonary artery (PA) annulus, z- scores, and RVOT gradients were not recorded which are important for approach of the treatment.
| References|| |
Dodge-Khatami A, Miller OI, Anderson RH, Goldman AP, Gil-Jaurena JM, Elliott MJ, et al
. Surgical substrates of postoperative junctional ectopic tachycardia in congenital heart defects. J Thorac Cardiovasc Surg 2002;123:624-30.
Vignati G, Mauri L, Figini A, Pomè G, Pellegrini A. Immediate and late arrhythmia in patients operated on for tetralogy of Fallot. Pediatr Med Chir 1998;20:3-6.
Parry AJ, McElhinney DB, Kung GC, Reddy VM, Brook MM, Hanley FL. Elective primary repair of acyanotic tetralogy of Fallot in early infancy: Overall outcome and impact on the pulmonary valve. J Am Coll Cardiol 2000;36:2279-83.
Paul T, Ziemer G, Luhmer L, Bertram H, Hecker H, Kallfelz HC. Early and late atrial dysrhythmias after modified Fontan operation. Pediatr Med Chir 1998;20:9-11.
Zampi JD, Hirsch JC, Gurney JG, Donohue JE, Yu S, LaPage MJ, et al.
Junctional ectopic tachycardia after infant heart surgery: Incidence and outcomes. Pediatr Cardiol 2012;33:1362-9.
Mildh L, Hiippala A, Rautiainen P, Pettila V, Sairanen H, Happonen JM. Junctional ectopic tachycardia after surgery for congenital heart disease: Incidence, risk factors and outcome. Eur J Cardiothorac Surg 2011;39:75-80.
Makhoul M, Oster M, Fischbach P, Das S, Deshpande S. Junctional ectopic tachycardia after congenital heart surgery in the current surgical era. Pediatr Cardiol 2013;34:370-4.
Mahmouda AB, Tantawy AE, Kouatlic AA, Baslaima GM. Propranolol: A new indication for an old drug in preventing postoperative junctional ectopic tachycardia after surgical repair of Tetralogy of Fallot. Interact Cardiovasc Thorac Surg 2008;7:184-7.
Mee RB. Surgical substrates of postoperative junctional ectopic tachycardia in congenital heart defects. J Thorac Cardiovasc Surg 2002;123:615-6.
Walsh EP, Saul JP, Sholler GF, Triedman JK, Jonas RA, Mayer JE, et al
. Evaluation of staged treatment protocol for rapid automatic junctional tachycardia after operation for congenital heart disease. J Am Coll Cardiol 1997;29:1046-53.
Hoffman TM, Bush DM, Wernovsky G, Cohen MI, Wieand TS, Gaynor JW, et al
. Postoperative junctional ectopic tachycardia in children: Incidence, risk factors and treatment. Ann Thorac Surg 2002;74:1607-11.
Gillette PC. Diagnosis and management of postoperative junctional ectopic tachycardia. Am Heart J 1989;118:192-4.
Ponce FE, Williams LC, Webb HM, Riopel DA, Hohn AR. Propranolol palliation of tetralogy of Fallot: Experience with long-term drug treatment in pediatric patients. Pediatrics 1973;52:100-8.
Garson A Jr, Gillette PC, McNamara DG. Propranolol: The preferred palliation for tetralogy of Fallot. Am J Cardiol 1981;47:1098-104.
Cumming GR, Carr W. Hemodynamic effects of propranolol in patients with Fallot′s tetralogy. Am Heart J 1967;74:29-36.
Plumpton K, Justo R, Haas N. Amiodarone for post-operative junctional ectopic tachycardia. Cardiol Young 2005;15:13-8.
Collins KK, Van Hare GF, Kertesz NJ, Law IH, Bar-Cohen Y, Dubin AM, et al
. Pediatric nonpost-operative junctional ectopic tachycardia: Medical management and interventional therapies. J Am Coll Cardiol 2009;53:690-7.
Sarubbi B, Vergara P, D′Alto M, Calabro R. Congenital junctional ectopic tachycardia: Presentation and outcome. Indian Pacing Electrophysiol J 2003;3:143-7.
Chrysostomou C, Sanchez-de-Toledo J, Wearden P, Jooste EH, Lichtenstein SE, Callahan PM, et al.
Perioperative use of dexmedetomidine is associated with decreased incidence of ventricular and supraventricular tachyarrhythmia′s after congenital cardiac operations. Ann Thorac Surg 2011;92:964-72.
Manrique AM, Arroyo M, Lin Y, El Khoudary SR, Colvin E, Lichenstein S, et al
. Magnesium supplementation during cardiopulmonary bypass to prevent junctional ectopic tachycardia after pediatric cardiac surgery: A randomized controlled study. J Thorac Cardiovasc Surg 2010;139:162-9.
Dorman BH, Sade RM, Burnette JS, Wiles HB, Pinosky ML, Reeves ST, et al
. Magnesium supplementation in the prevention of arrhythmias in paediatric patients undergoing surgery for congenital heart defects. Am Heart J 2000;139:522-8.
Yabek SM, Berman W Jr, Dillon T. Electrophysiologic effects of propranolol on sinus node function in children. Am Heart J 1982;104:612-6.
Carmona MJ, Malbouisson LM, Pereira VA, Bertoline MA, Omosako CE, Le Bihan KB, et al
. Cardiopulmonary bypass alters the pharmacokinetics of propranolol in patients undergoing cardiac surgery. Braz J Med Biol Res 2005;38:713-21.
Plachetka JR, Salomon NW, Copeland JG. Plasma propranolol before, during, and after cardiopulmonary bypass. Clin Pharmacol Ther 1981;30:745-51.
Wood M, Shand DG, Wood AJ. Propranolol binding in plasma during cardiopulmonary bypass. Anesthesiology 1979;51:512-6.
Roth RA, Wiersma DA. Role of the lung in total body clearance of circulating drugs. Clin Pharmacokinet 1979;4:355-67.
Dodge-Khatami A, Miller OI, Anderson RH, Gil-Jaurena JM, Goldman AP, de Leval MR. Impact of junctional ectopic tachycardia on postoperative morbidity following repair of congenital heart defects. Eur J Cardiothorac Surg 2002;21:255-9.
[Table 1], [Table 2], [Table 3]