| Abstract|| |
Objective: The objective of this study was to assess the effectiveness of pre-emptive dexmedetomidine versus amiodarone in preventing junctional ectopic tachycardia (JET) in pediatric cardiac surgery. Design: This is a prospective, controlled study. Setting: This study was carried out at a single university hospital. Subjects and Methods: Ninety patients of both sexes, American Society of Anesthesiologists Physical Status II and III, age range from 2 to 18 years, and scheduled for elective cardiac surgery for congenital and acquired heart diseases were selected as the study participants. Interventions: Patients were randomized into three groups (30 each). Group I received dexmedetomidine 1 mcg/kg diluted in 100 ml of normal saline intravenously (IV) over a period of 20 min, and the infusion was completed 10 min before the induction followed by a 0.5 mcg/kg/h infusion for 72 h postoperative, Group II received amiodarone 5 mg/kg diluted in 100 ml of normal saline IV over a period of 20 min, and the infusion was completed 10 min before the induction followed by a 10–15 mcg/kg/h infusion for 72 h postoperative, and Group III received 100 ml of normal saline IV. Primary outcome was the incidence of postoperative JET. Secondary outcomes included vasoactive-inotropic score, ventilation time (VT), pediatric cardiac care unit stay, hospital length of stay, and perioperative mortality. Measurements and Main Results: The incidence of JET was significantly reduced in Group I and Group II (P = 0.004) compared to Group III. Heart rate while coming off from cardiopulmonary bypass (CPB) was significantly low in Group I compared to Group II and Group III (P = 0.000). Mean VT, mean duration of Intensive Care Unit stay, and length of hospital stay (day) were significantly short (P = 0.000) in Group I and Group II compared to Group III (P = 0.000). Conclusion: Perioperative use of dexmedetomidine and amiodarone is associated with significantly decreased incidence of JET as compared to placebo without significant side effects.
Keywords: Amiodarone; Children; Dexmedetomidine; Junctional ectopic tachycardia; Postoperative arrhythmia
|How to cite this article:|
El-Shmaa NS, El Amrousy D, El Feky W. The efficacy of pre-emptive dexmedetomidine versus amiodarone in preventing postoperative junctional ectopic tachycardia in pediatric cardiac surgery. Ann Card Anaesth 2016;19:614-20
|How to cite this URL:|
El-Shmaa NS, El Amrousy D, El Feky W. The efficacy of pre-emptive dexmedetomidine versus amiodarone in preventing postoperative junctional ectopic tachycardia in pediatric cardiac surgery. Ann Card Anaesth [serial online] 2016 [cited 2019 Sep 23];19:614-20. Available from: http://www.annals.in/text.asp?2016/19/4/614/191564
| Introduction|| |
The incidence of arrhythmias, especially JET, is high after pediatric cardiac surgery and is difficult to control., JET is associated with an increased risk of postoperative hemodynamic deterioration, increased length of Intensive Care Unit (ICU) and hospital stays, health-care costs, and mortality rate and hence, preventive measures to decrease the incidence of this arrhythmia are recommended.,
The current treatment regimens include removal of exacerbating factors, use of beta blocker, cooling of patients to maintain core temperature around 35°C, and use of magnesium sulfate and amiodarone,,,, but ideal is to prevent it. None of the current medications are useful in preventing or reducing the incidence of JET in cardiac surgery.
Dexmedetomidine is used as a sedative and analgesic in pediatric ICUs. It is a selective α-2 adrenoceptor agonist which has sedative, analgesic, and anxiolytic effects that are associated with opioid and anesthetic-sparing effects.,,, The agonistic effect on the α-2 adrenoceptors modifies the release of catecholamine, leading to a sympatholytic action with negative chronotropic and dromotropic effects.,,, These sympatholytic actions are being studied as a therapeutic option for the prevention and treatment of various perioperative tachyarrhythmias.,, These arrhythmias lead to significant hemodynamic instability and increase morbidity, especially after cardiopulmonary bypass (CPB) time. There are few studies of dexmedetomidine usage to prevent JET after cardiac surgery in children.,,
Amiodarone is a class III antiarrhythmic drug that prolongs repolarization and refractory period of atrial, nodal, and ventricular tissues, with both beta blocker-like and potassium channel blocker-like effects. Its action in JET may be due to its inhibition of abnormal automaticity and increase in the refractory period of the atrioventricular (AV) node and His-Purkinje system. Hence, amiodarone has been reported to be one of the most effective agents in managing JET after cardiac surgery. While, amiodarone has been proved to be effective and safe in preventing postoperative atrial fibrillation in adults after cardiac surgery in many studies,, its effect in preventing postoperative arrhythmias in pediatrics is still needs to be confirmed.
The objective of this study was to assess the effectiveness of pre-emptive dexmedetomidine versus amiodarone in preventing junctional ectopic tachycardia (JET) in pediatric cardiac surgery and to study its impact on various outcomes such as vasoactive-inotropic score (VIS), ventilation time (VT), length of pediatric cardiac care unit (PCCU) stay, hospital length of stay, and mortality rate.
| Subjects and Methods|| |
This is a prospective controlled study conducted at the Tanta University Hospital on ninety patients of both sexes during the period from October 2010 to March 2014 after obtaining approval from the hospital's Ethical Committee, and a written informed consent of the parents was obtained. The CONSORT 2010 statement was followed in reporting this study.
Inclusion criteria were participants with the American Society of Anesthesiologists (ASA) Physical Status II–III and age between 2 and 18 years scheduled for elective cardiac surgery under general anesthesia.
Exclusion criteria were participants of age <2 years, weight <2 kg, known allergy to dexmedetomidine or amiodarone drugs, chronic heart failure, liver disease, significant baseline neurologic impairment that prevents the evaluation of sedative and analgesic agents, permanent pacemaker, a history of arrhythmias within the last 6 months, usage of antiarrhythmic medications and beta blockers within the last 72 h, use of amiodarone or dexmedetomidine within the last 30 days, use of dexmedetomidine for ≤12 h after the end of CPB, and if dexmedetomidine or amiodarone was used in the control group as a rescue agent for arrhythmia.
Patients were allocated into three groups of 30 patients each according to the drug used. Group I received dexmedetomidine 1 mcg/kg diluted in 100 ml of normal saline intravenously (IV) over a period of 20 min, and the infusion was completed 10 min before the induction followed by a 0.5 mcg/kg/h infusion for 72 h postoperative (Precedex; Hospira Worldwide, Lake Forest, IL, USA). Group II received amiodarone 5 mg/kg diluted in 100 ml of normal saline IV over a period of 20 min, and the infusion was completed 10 min before the induction followed by a 10–15 mcg/kg/h infusion for 72 h postoperative (Ronecard; T3A, Egypt), and Group III received 100 ml of normal saline IV. The decision whether patients would receive dexmedetomidine, amiodarone, or not was a clinical decision and based entirely on the preference of a primary cardiac anesthesiologist. Top-up bolus doses of fentanyl and midazolam were given according to the need in the study groups. Sedation was monitored with bispectral index (BIS). Data collection was done in the operative room (OR) and in pediatric cardiac Intensive Care Unit (PCICU).
Anesthesia, cardiopulmonary bypass, and surgical management
After premedication with injection midazolam 0.1 mg/kg and injection ketamine 1 mg/kg IV in the preoperative waiting area, all children were shifted to the OR. Endotracheal intubation was done after giving fentanyl and rocuronium injection. Dexmedetomidine and amiodarone infusions were started in standard doses as mentioned above. All the surgeries were conducted with similar techniques by the same team of surgeons, anesthesiologist, and perfusionist, during the study period under standard CPB techniques. Rescue inotropes were added depending on the requirement.
Standard 12-lead electrocardiogram (ECG) was recorded in all patients preoperatively and then immediately after surgery in the PCICU. Continuous monitoring of ECG, BIS, arterial blood pressure, central venous pressure, end-tidal carbon dioxide, and oxygen saturation was done with Drager monitors.
Diagnostic criteria for JET included the following:
- Tachycardia with QRS similar to sinus rhythm QRS
- A ventricular rate more than 170 beats/min
- AV dissociation with or without hemodynamic compromise
- A ventricular rate faster than the atrial rate.
Early onset postoperative JET was defined as the presence of JET during the first 72 h postoperatively. Continuous ECG monitoring was used continuously in the PCCU. Standard 12-lead ECG was registered in all patients preoperatively and at the time of PCCU admission. When JET was detected on the ECG monitor, this was also documented with a standard ECG strip.
Primary outcome was the incidence of postoperative JET. Secondary outcomes included VIS, duration of mechanical ventilation, PCCU stay, hospital length of stay, and mortality rate. Episodes of sinus bradycardia and hypotension (values ≤5% for age, or bradycardia requiring temporary atrial pacing) were recorded for the analysis.
Inotropic score = (dopamine × 1) + (dobutamine × 1) + (adrenaline × 100) + (noradrenaline × 100) + (milrinone × 10). Dosages of above drugs were in mcg/kg/min.
Sample size calculation was performed before patient recruitment, based on a previous study,, and also it was calculated by power analysis, using a two-sample t-test, with a two-sided Type I error of 5% (α = 0.05) and power at 80.37 (α = 0.19). Therefore, ninety patients were included in the study. SPSS version 11.0.1 (SPSS Inc., Chicago, IL, USA) for Windows was used for statistical analysis. All results were presented in the form of mean ± standard deviation. Multiple analyses of variance (ANOVA) was used to compare the data of the three groups, and Bonferroni test was used after ANOVA, while paired t-test was used to compare data within the same group. Power of significance (P < 0.05) was considered statistically significant.
| Results|| |
[Figure 1] shows the flow diagram for this study, in which 100 patients were assessed for eligibility and 90 patients were included in the study. The results of the ninety patients were analyzed.
|Figure 1: The randomized trial flow diagram, including enrollment, intervention allocation, and analysis|
Click here to view
The preoperative variables including gender and ASA II/III distribution, mean age, mean weight, and preoperative heart rate (HR) were recorded, and nonsignificant differences were found between the three groups (P > 0.05) [Table 1].
There was no significant difference between the three groups with regard to CPB time (cardiopulmonary) and aortic cross-clamp (AXC). HR while coming off from CPB was significantly lower in Group I compared to Group III and Group II (P = 0.000) [Table 2].
The incidence of postoperative JET was 6.66% (2 out of 30) in Group I and Group II, while it was 33.33% (10 out of 30) in Group III, and this difference was statistically significant (P = 0.004). VIS was significantly lower in Group I and Group II compared to Group III (P = 0.000) [Table 3].
Mean VT, mean duration of PCCU stay, and length of hospital stay (day) were significantly reduced (P = 0.000) in Group I and Group II compared to Group III. There was one mortality in Group I and Group II whereas there were two mortalities in Group III in the perioperative period, and it was found to be comparable in the three groups (P = 0. 776) [Table 3].
Bradycardia occurred in three patients and hypotension occurred in two patients after dexmedetomidine, amiodarone, or placebo administration; there was no significant difference with regard to the incidence of bradycardia (P = 0.368) and the incidence of hypotension (P = 0.603) between the three groups [Table 3].
| Discussion|| |
During the postoperative period, JET is one of the resistant and life-threatening arrhythmias that is difficult to manage. Currently available antiarrhythmic drugs are poorly tolerated during the post-CPB period. To the best of our knowledge, to date, the present study is the first to assess the effectiveness of pre-emptive dexmedetomidine versus amiodarone in preventing JET in pediatric cardiac surgery and to study its impact on various outcomes such as VIS, VT, PCCU stay, hospital length of stay, and mortality rate.
The major finding of the current study is that prophylactic dexmedetomidine and amiodarone decreased the incidence of JET in pediatric patients undergoing cardiac surgery from 33.33% in Group III to 6.6% in Group I and Group II, which was in accordance with the previous studies.,
Sedatives and analgesics are necessary for the management of ventilated pediatric cardiac patients in the postoperative period. There are multiple choices, but they have their own adverse effects such as respiratory depression, hypotension, bradycardia, tolerance, and dependence. We are still to have an ideal sedative and analgesic for ICU in pediatric cardiac patients. Dexmedetomidine is recently being used in many ICUs because of its near ideal actions such as no respiratory depression, good sedative, modest analgesic, and anxiolytic actions.,,, Its main adverse effect is bradycardia; however, this adverse effect is being studied for the prevention and control of different arrhythmias such as JET after cardiac surgery.
Kamibayashi et al. found that dexmedetomidine can prevent epinephrine/halothane-induced ventricular tachycardia and suggested that the antiarrhythmic action of dexmedetomidine is due to activation of the α-2 adrenoreceptors. However, other studies suggested that it is produced through its action on cerebral imidazoline receptors and its effect on the vagal nerve.
Wijeysundera et al. investigated the effects of alpha (2)-adrenergic agonists on perioperative mortality and cardiovascular complications in adults undergoing surgery, and in contrast to the previously discussed studies, they found that the use of α-2 agonists, in general, had no effect on the incidence of arrhythmias.
The present study found that HR while coming off from CPB was significantly lower in Group I compared to Group III and Groups II (P = 0.000), and this reduced HR while coming off from CPB is extended to reduced the incidence of JET. These results are in consistent with those obtained by Hammer et al. who found that dexmedetomidine decreased both sinus and AV nodal function that are responsible for the reduced incidence of JET.
The present study showed that VIS was significantly less in Group I and Group II compared to Group III, with P = 0.000. Hence, Group I required less inotropes compared to Group II and Group III. This reduced inotropic requirement in dexmedetomidine group can be because reduced incidence of JET in that group or, in other words, high incidence of JET in Group III required more inotropes. Similar findings have previously been reported in a study done by Kadam et al.
We found that dexmedetomidine and amiodarone prophylaxis significantly shortened, VT, postoperative PCCU, and hospital stay with P = 0.000 and consequently reduced the cost of surgery, but they did not affect the incidence of mortality with P = 0.776. This was achieved without significant side effects such as bradycardia and hypotension (only five cases, it was not significant and not necessitating the stoppage of studied drugs). These results are in consistent with those obtained by Imamura et al. who found no postoperative bradycardia and hypotension at all after prophylactic IV amiodarone and this can be explained by smaller number of their patients, the usage of lower doses of IV amiodarone, and shorter duration of their study.
Limitations of the current study include the nature of a nonrandomized methodology that could not establish direct causal relationships with certainty. This study involves a relatively small number of patients. Our study period was only 72 h and thus, we may have missed arrhythmias that occurred afterward. Supplemental data such as ventricular function were not available.
| Conclusion|| |
Perioperative use of dexmedetomidine and amiodarone is associated with significantly decreased incidence of JET as compared to placebo without significant side effects.
The authors would like to thank the nurses at the cardiothoracic theater of the Tanta University Hospital, Tanta, for their assistance in conducting the study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Mildh L, Hiippala A, Rautiainen P, Pettilä 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.
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 tachyarrhythmias after congenital cardiac operations. Ann Thorac Surg 2011;92:964-72.
Chrysostomou C, Di Filippo S, Manrique AM, Schmitt CG, Orr RA, Casta A, et al.
Use of dexmedetomidine in children after cardiac and thoracic surgery. Pediatr Crit Care Med 2006;7:126-31.
Wijeysundera DN, Naik JS, Beattie WS. Alpha-2 adrenergic agonists to prevent perioperative cardiovascular complications: A meta-analysis. Am J Med 2003;114:742-52.
Chrysostomou C, Sanchez De Toledo J, Avolio T, Motoa MV, Berry D, Morell VO, et al.
Dexmedetomidine use in a pediatric cardiac intensive care unit: Can we use it in infants after cardiac surgery? Pediatr Crit Care Med 2009;10:654-60.
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.
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.
Walsh EP, Saul JP, Sholler GF, Triedman JK, Jonas RA, Mayer JE, et al.
Evaluation of a 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.
Kamibayashi T, Maze M. Clinical uses of alpha2-adrenergic agonists. Anesthesiology 2000;93:1345-9.
Hall JE, Uhrich TD, Barney JA, Arain SR, Ebert TJ. Sedative, amnestic, and analgesic properties of small-dose dexmedetomidine infusions. Anesth Analg 2000;90:699-705.
Jaakola ML, Salonen M, Lehtinen R, Scheinin H. The analgesic action of dexmedetomidine – A novel alpha 2-adrenoceptor agonist – In healthy volunteers. Pain 1991;46:281-5.
Venn M, Newman J, Grounds M. A phase II study to evaluate the efficacy of dexmedetomidine for sedation in the medical intensive care unit. Intensive Care Med 2003;29:201-7.
Scheinin B, Lindgren L, Randell T, Scheinin H, Scheinin M. Dexmedetomidine attenuates sympathoadrenal responses to tracheal intubation and reduces the need for thiopentone and peroperative fentanyl. Br J Anaesth 1992;68:126-31.
Talke P, Richardson CA, Scheinin M, Fisher DM. Postoperative pharmacokinetics and sympatholytic effects of dexmedetomidine. Anesth Analg 1997;85:1136-42.
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.
Bagshaw SM, Galbraith PD, Mitchell LB, Sauve R, Exner DV, Ghali WA. Prophylactic amiodarone for prevention of atrial fibrillation after cardiac surgery: A meta-analysis. Ann Thorac Surg 2006;82:1927-37.
Buckley MS, Nolan PE Jr., Slack MK, Tisdale JE, Hilleman DE, Copeland JG. Amiodarone prophylaxis for atrial fibrillation after cardiac surgery: Meta-analysis of dose response and timing of initiation. Pharmacotherapy 2007;27:360-8.
Davidson J, Tong S, Hancock H, Hauck A, da Cruz E, Kaufman J. Prospective validation of the vasoactive-inotropic score and correlation to short-term outcomes in neonates and infants after cardiothoracic surgery. Intensive Care Med 2012;38:1184-90.
Kadam SV, Tailor KB, Kulkarni S, Mohanty SR, Joshi PV, Rao SG. Effect of dexmeditomidine on postoperative junctional ectopic tachycardia after complete surgical repair of tetralogy of Fallot: A prospective randomized controlled study. Ann Card Anaesth 2015;18:323-8.
Imamura M, Dossey AM, Garcia X, Shinkawa T, Jaquiss RD. Prophylactic amiodarone reduces junctional ectopic tachycardia after tetralogy of Fallot repair. J Thorac Cardiovasc Surg 2012;143:152-6.
Kamibayashi T, Mammoto T, Hayashi Y, Yamatodani A, Takada K, Sasaki S, et al.
Further characterization of the receptor mechanism involved in the antidysrhythmic effect of dexmedetomidine on halothane/epinephrine dysrhythmias in dogs. Anesthesiology 1995;83:1082-9.
Hammer GB, Drover DR, Cao H, Jackson E, Williams GD, Ramamoorthy C, et al.
The effects of dexmedetomidine on cardiac electrophysiology in children. Anesth Analg 2008;106:79-83.
Nagat S El-Shmaa
Department of Anesthesia and Surgical ICU, Faculty of Medicine, Tanta University, Tanta
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3]