| Abstract|| |
Introduction: Dexmedetomidine is an alpha-2 agonist used for conscious sedation. It has also been shown to have a myocardial protective effect in off-pump coronary artery bypass patients. The aim of the study was to assess the effect of dexmedetomidine for myocardial protection in percutaneous coronary interventional patients. Methodology: A total of 60 patients (group dexmedetomidine, n = 30 and group normal saline, n = 30) were enrolled in the study. Dexmedetomidine infusion (1 mcg/kg) over 15 min was given as a loading dose after coronary angiography in group dexmedetomidine (D) while normal saline was given in the control group (C) and later maintenance infusion was started at 0.5 mcg/kg/h in both the groups. Coronary vessel diameter was noted before (T0) and after (T1) loading dose of dexmedetomidine/saline in each group. Troponin T (Trop T) values were noted at baseline (T0), 6 h (T2), 12 h (T3) and 24 h (T4) after starting the loading dose. Hemodynamic variables (heart rate [HR] and blood pressure) were monitored at T0, T1, and at regular intervals till 2 h postprocedure. Results: Coronary vessel diameter and HR significantly decreased in group D as compared to control group (P < 0.05) whereas the decrease in Trop T at 6 h, 12 h, and 24 h were not statistically significant between the two groups. Conclusion: Dexmedetomidine decreases the coronary vessel diameter, but maintains the myocardial oxygen demand-supply ratio by decreasing the HR. The decrease in Trop T is statistically insignificant at the doses used.
Keywords: Dexmedetomidine; Percutaneous coronary intervention; Troponin
|How to cite this article:|
Kundra TS, Nagaraja P S, Singh NG, Dhananjaya M, Sathish N, Manjunatha N. Effect of dexmedetomidine on diseased coronary vessel diameter and myocardial protection in percutaneous coronary interventional patients. Ann Card Anaesth 2016;19:394-8
|How to cite this URL:|
Kundra TS, Nagaraja P S, Singh NG, Dhananjaya M, Sathish N, Manjunatha N. Effect of dexmedetomidine on diseased coronary vessel diameter and myocardial protection in percutaneous coronary interventional patients. Ann Card Anaesth [serial online] 2016 [cited 2021 Aug 4];19:394-8. Available from: https://www.annals.in/text.asp?2016/19/3/394/185517
| Introduction|| |
Myocardial injury in acute myocardial infarction (MI) is due to both ischemic as well as reperfusion injury. Reperfusion can cause hyperkalemia,  arrhythmias and a rise in cardiac enzymes (Troponin I and T and creatinine phosphokinase-MB (CPK-MB)). A number of strategies have been used to prevent lethal myocardial reperfusion injury in patients undergoing percutaneous coronary interventional (PCI) procedures. Mechanical interventions include remote ischemic preconditioning, therapeutic hypothermia and therapeutic hyperoxemia, whereas pharmacological interventions include adenosine, anti-inflammatory agents, atrial natriuretic peptide, atorvastatin, erythropoietin, glucose insulin potassium therapy and sodium nitrite. 
Dexmedetomidine is a selective alpha-2 agonist which may shrink the coronary arteries and reduce coronary blood flow. , But at the same time, dexmedetomidine reduces heart rate (HR) and consequently the myocardial oxygen demand. Hence, we postulate that dexmedetomidine should maintain the myocardial oxygen demand-supply ratio. In addition, dexmedetomidine results in sympathetic blockade, as it affects the alpha-2 receptors in the central nervous system and restrains the release of central sympathetic neurotransmitter (predominantly norepinephrine).  Patients undergoing PCI have a lot of stress response and hence, dexmedetomidine may be useful to alleviate anxiety which can also decrease the oxygen demand and improve the oxygen demand-supply ratio.
Dexmedetomidine has been shown to have a protective effect on myocardial ischemia/reperfusion (I/R) injury in rats , and decreases the incidence of arrhythmias. However, there is limited literature on the effect of dexmedetomidine during I/R injury in PCI patients.
Hence, the aim of the study was to assess the effect of dexmedetomidine on coronary vessel diameter and myocardial protective effect in patients undergoing PCI.
| Methodology|| |
After Institutional Ethics Committee approval, a prospective double-blind randomized controlled trial was conducted. A sample size of 60 was calculated based on a previous study. 
Sixty patients undergoing elective PCI for acute MI with single vessel disease were randomized into Group D (dexmedetomidine) n = 30 and Group C (control) n = 30. Patients above the age of 70 years, ejection fraction (EF) of <40% and in cardiogenic shock were excluded from the study. All these patients were adequately beta-blocked in the ward. Patients were randomized on the basis of computer-generated randomization table. The randomization scheme was generated by using the website Randomization.com http://www.randomization.com. The computer-generated group number (D or C) was enclosed in serially numbered closed opaque envelope. A person not related to the study was asked to open the closed envelope containing computer-generated group number. The groups were as follows:
Immediately after coronary angiogram (T0), a baseline troponin T (Trop T) was sent for analysis and coronary vessel diameter was measured immediately distal to the obstruction in the diastolic phase. Then, dexmedetomidine or 0.9% NaCl infusion was started. After the loading dose and before initiation of coronary angioplasty (T1), coronary diameter was again measured in the same view to see the effect of dexmedetomidine on the coronary diameter. The infusion of dexmedetomidine was continued until 30 min postprocedure. Trop T was analysed at 6 h (T2), 12 h (T3), and 24 h (T4) after starting the loading dose.
- Group D: Injection dexmedetomidine 1 mcg/kg was administered over 15 min as a loading dose and then 0.5 mcg/kg/h as maintenance infusion
- Group C: Injection 0.9% NaCl (started and maintained at the same rate as calculated for group D).
HR and blood pressure (BP) were monitored every 5 min during the procedure and every 10 min postprocedure for 2 h.
Electrocardiogram (ECG) was recorded preprocedure, postprocedure, at 24 h, and 72 h for any new ECG changes and/or arrhythmias.
Statistical analysis was performed using MedCalc software version 220.127.116.11.(Ostend, Belgium). Intragroup analysis were done using paired Student's t-test, and unpaired Student's t-test was done for analysis between the two groups. Hemodynamic variables and Trop T values were expressed as mean ± SD. P < 0.05 was considered significant.
| Results|| |
Thirty patients were included in each of the two groups. In group D, there were 18 males and 12 females, whereas in group C, there were 16 males and 14 females. All the patients were aged between 40 and 60 years. In group D, 25 patients had EF between 40 and 50% and five patients had EF between 51% and 60%. In Group C, 23 patients had EF between 40% and 50% and seven patients had EF between 51% and 60%.
The diameter of the coronary vessel decreased significantly by around 14% after loading dose of dexmedetomidine infusion (P = 0.000) whereas no such significant change was observed in the control group (P = 0.25) [Table 1].
|Table 1: Diameter of the coronary vessel before and after administering loading dose of dexmedetomidine/normal saline |
Click here to view
HR also decreased significantly by around 13% after loading dose of dexmedetomidine infusion (P = 0.000), while the change in HR was not significant in the control group (P = 0.59) [Table 2].
|Table 2: Heart rate before and after administering loading dose of dexmedetomidine/normal saline |
Click here to view
There was a statistically significant decrease in systolic blood pressure (SBP) and diastolic blood pressure (DBP) after administering loading dose of dexmedetomidine, but no such decrease was observed in the control group [Table 3]a and b.
There was no statistically significant difference in the Trop T values at baseline (T0), 6 h (T2), 12 h (T3), and at 24 h (T4) between dexmedetomidine group and control group [Table 4].
|Table 4: Trop T values (ng/ml) at baseline, 6 h, 12 h, and 24 h after initiation of the drug |
Click here to view
Three patients in the control group had arrhythmias during the procedure and postprocedure, while none in the dexmedetomidine group had arrhythmias.
| Discussion|| |
Reperfusion injury is defined as damage to the tissue caused when blood supply is restored to the ischemic or hypoxic area after a certain period. Similar type of injury occurs in the myocardium after an acute MI treated by PCI or fibrinolytic therapy. ,,
Reperfusion is associated with microvascular injury, particularly due to increased permeability of capillaries and arterioles. Activated endothelial cells produce more reactive oxygen free radicals but less nitric oxide after reperfusion. This imbalance causes an inflammatory response which is partially responsible for the damage caused by reperfusion injury.  White blood cells (WBCs) are carried to the reperfused area by restoration of blood flow which causes a release of inflammatory factors such as interleukins and free radicals.  These cause damage to the cellular proteins, DNA, and the plasma membrane, which may cause further release of more free radicals. These mediators may also act indirectly in redox signaling to initiate apoptosis. WBC may also obstruct the small capillaries by binding to their endothelium, worsening the ischemia.  Furthermore, the ischemic tissue has decreased free radical scavengers, which results in further tissue damage after reperfusion.
Other mechanisms postulated in reperfusion injury include calcium overload and depletion of high energy phosphate stores. ,,
Hyperkalemia,  arrhythmias, and rise in cardiac enzymes (Trop I and T and CPK-MB) may help us in recognizing this reperfusion injury.
Dexmedetomidine being a selective alpha-2 agonist may cause coronary vasoconstriction. Yoshitomi et al. and Okada et al. showed that dexmedetomidine has a direct dose-dependent cardioprotective effect on reperfusion injury and high dose of dexmedetomidine had favorable subendocardial-to-subepicardial blood flow ratio resulting in better functional recovery from myocardial stunning.
Dexmedetomidine is an ideal sedative agent in cardiac patients  as it is a sympatholytic, reduces HR, and consequently the myocardial oxygen demand. It causes conscious sedation in which the patient is arousable when stimulated. Hence, it is beneficial to use dexmedetomidine for sedating the anxious cardiac PCI patients.
In the present study, the SBP and DBP have shown a statistically significant decrease in group D. This can be attributed to sympatholysis and anxiolysis.  However, the decrease in BP was never <20% of the baseline.
There was also a significant decrease in the coronary vessel diameter. However, there was no significant change in the levels of Trop T. Hence, the authors infer that myocardial damage has not occurred with the decrease in coronary vessel diameter in the dexmedetomidine group. Although the blood flow has decreased due to coronary vasoconstriction, simultaneously, the demand has also decreased by a significant decrease in HR caused by dexmedetomidine. Hence, dexmedetomidine maintains the demand-supply ratio in spite of decreasing the coronary vessel diameter.
In the present study, three patients of control group had arrhythmias during the procedure and postprocedure, while none in the dexmedetomidine group had arrhythmias. There is a probability that dexmedetomidine could have prevented arrhythmias caused by I/R in the study group, but the sample size is too small to conclude this.
Chi et al. found that dexmedetomidine reduces myocardial damage in patients undergoing off-pump coronary artery bypass graft surgery as noted by a decrease in the myocardial enzymes in the dexmedetomidine group as compared to the control group. In the present study, there was no significant decrease in Trop T levels in patients who were given the same dose of dexmedetomidine as in the above study. This could be due to various reasons. First, the dosage of dexmedetomidine used was based on previous studies done in cardiac surgical patients. The dosage required in PCI patients may be different because of shorter duration of the procedure. The total duration and dosage of dexmedetomidine were probably lesser in the present study as compared to the cardiac surgical patients.  Secondly, the extent of myocardial damage is probably lesser in PCI patients as compared to cardiac surgical patients. The myocardial damage caused by surgical handling is more due to the duration of surgery, increased inflammation, vasopressors and surgical stress. Thirdly, the sample size was calculated based on previous surgical studies. Maybe a larger sample size was required in PCI patients. Further studies with a different dosage and/or duration with larger sample size is required to validate the myocardial protective effect in I/R injury.
| Conclusion|| |
Dexmedetomidine is an effective drug used for conscious sedation in anxious patients undergoing PCI. , The role of dexmedetomidine in myocardial protection of PCI patients could not be proved with respect to cardiac enzymes. However, even though dexmedetomidine decreased the coronary vessel diameter, it had also decreased the HR. Thus, the authors assume that it maintains the myocardial oxygen supply-demand ratio, leading to a myocardial protective effect.
The authors would like to acknowledge the help provided by Dr. C. N. Manjunath, Director and HOD, Dept. of Cardiology, Sri Jayadeva Institute of Cardiovascular Sciences and Research, Bengaluru.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Atlee JL. Complications in Anesthesia. 2 nd
ed. Philadelphia, PA: Elsevier Health Sciences; 2007. p. 55.
Hausenloy DJ, Yellon DM. Myocardial ischemia-reperfusion injury: A neglected therapeutic target. J Clin Invest 2013;123:92-100.
Willigers HM, Prinzen FW, Roekaerts PM. Comparison of the effects of dexmedetomidine and esmolol on myocardial oxygen consumption in dogs. Eur J Anaesthesiol 2004;21:957-66.
Snapir A, Posti J, Kentala E, Koskenvuo J, Sundell J, Tuunanen H, et al.
Effects of low and high plasma concentrations of dexmedetomidine on myocardial perfusion and cardiac function in healthy male subjects. Anesthesiology 2006;105:902-10.
Penttilä J, Helminen A, Anttila M, Hinkka S, Scheinin H. Cardiovascular and parasympathetic effects of dexmedetomidine in healthy subjects. Can J Physiol Pharmacol 2004;82:359-62.
Kocoglu H, Karaaslan K, Gonca E, Bozdogan O, Gulcu N. Precondition in effects of dexmedetomidine on myocardial ischemia/reperfusion injury in rats. Curr Ther Res Clin Exp 2008;69:150-8.
Kip G, Çelik A, Bilge M, Alkan M, Kiraz HA, Özer A, et al.
Dexmedetomidine protects from post-myocardial ischaemia reperfusion lung damage in diabetic rats. Libyan J Med 2015;10:27828.
Ren J, Zhang H, Huang L, Liu Y, Liu F, Dong Z. Protective effect of dexmedetomidine in coronary artery bypass grafting surgery. Exp Ther Med 2013;6:497-502.
Simoons ML, Serruys PW, van den Brand M, Res J, Verheugt FW, Krauss XH, et al.
Early thrombolysis in acute myocardial infarction: Limitation of infarct size and improved survival. J Am Coll Cardiol 1986;7:717-28.
White HD, Norris RM, Brown MA, Takayama M, Maslowski A, Bass NM, et al.
Effect of intravenous streptokinase on left ventricular function and early survival after acute myocardial infarction. N Engl J Med 1987;317:850-5.
Sheehan FH, Doerr R, Schmidt WG, Bolson EL, Uebis R, von Essen R, et al.
Early recovery of left ventricular function after thrombolytic therapy for acute myocardial infarction: An important determinant of survival. J Am Coll Cardiol 1988;12:289-300.
Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol 2000;190:255-66.
Sharifi Z-N, Abolhassani F, Zarrindast MR, Movassaghi S, Rahimian N, Hassanzadeh G. Effects of FK506 on Hippocampal CA1 Cells Following Transient Global Ischemia/Reperfusion in Wistar Rat. Stroke Research and Treatment 2012;2012:809417. doi:10.1155/2012/809417.
Kwak YL. Reduction of ischemia during off-pump coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2005;19:667-77.
Opie LH. Cell death: Myocardial infarction. In: Opie LH, editor. The Heart: Physiology, From Cell to Circulation. 3 rd
ed. Philadelphia, PA: Lippincott-Raven Publishers; 1998. p. 543-61.
Opie LH. Oxygen lack: Ischemia and angina. In: Opie LH, editor. The Heart: Physiology, From Cell to Circulation. 3 rd
ed. Philadelphia, PA: Lippincott-Raven Publishers; 1998. p. 515-41.
Yoshitomi O, Cho S, Hara T, Shibata I, Maekawa T, Ureshino H, et al.
Direct protective effects of dexmedetomidine against myocardial ischemia-reperfusion injury in anesthetized pigs. Shock 2012;38:92-7.
Okada H, Kurita T, Mochizuki T, Morita K, Sato S. The cardioprotective effect of dexmedetomidine on global ischaemia in isolated rat hearts. Resuscitation 2007;74:538-45.
Dasta JF, Jacobi J, Sesti AM, McLaughlin TP. Addition of dexmedetomidine to standard sedation regimens after cardiac surgery: An outcomes analysis. Pharmacotherapy 2006;26:798-805.
Jalonen J, Hynynen M, Kuitunen A, Heikkilä H, Perttilä J, Salmenperä M, et al.
Dexmedetomidine as an anesthetic adjunct in coronary artery bypass grafting. Anesthesiology 1997;86:331-45.
Chi X, Liao M, Chen X, Zhao Y, Yang L, Luo A, et al.
Dexmedetomidine attenuates myocardial injury in off-pump coronary artery bypass graft surgery. J Cardiothorac Vasc Anesth 2016;30:44-50.
Cetin M, Birbicer H, Hallioglu O, Orekeci G. Comparative study between the effects of dexmedetomidine and propofol on cerebral oxygenation during sedation at pediatric cardiac catheterization. Annals of Cardiac Anaesthesia 2016;19:20-4.
Moshiri E, Modir H, Bagheri N, Mohammadbeigi A, Jamilian H, Eshrati B. Premedication effect of dexmedetomidine and alfentanil on seizure time, recovery duration, and hemodynamic responses in electroconvulsive therapy. Annals of Cardiac Anaesthesia 2016;19:263-8.
Tanveer Singh Kundra
Kothi No.184, Phase 4, Mohali- 160055, Punjab
Source of Support: None, Conflict of Interest: None
[Table 1], [Table 2], [Table 3], [Table 4]