Supraventricular tachycardias (SVTs) is the most common cardiac complications, and can frequently cause serious cardiovascular events and hemodynamic instability, leading to increased morbidity and mortality in the perioperative period. SVTs is associated with disorders of autonomic nervous regulation of cardiac activity, and reentrant excited. Dexmedetomidine (DEXm), a highly selective α2-RA, was initially used as sedative and anaesthetic adjuvants. The antiarrhythmic effect of DEXm in pediatric cardiac surgery and intubation reflex was observed in previous literature, suggesting that its antiarrhythmic effect in noncardiac surgery and adult patients needs to be further explored. Here, we designed the study to evaluate therapeutic effect of DEXm on SVTs in adult patients. Furthermore, we took full advantage of DXEm effects, such as bradycardia and the negative chronotropic effects of the heart (e.g. treat tachyarrhythmia). Given that the SVTs had proven to be difficult to control and had resulted in adverse effects, we chose to continuously infuse DEXm. Our results (Table 4 and Fig. 1) has demonstrated that DEXm had a good therapeutic effect and safety profile, and much few adverse effects for the treatment of SVTs. Heart rates started to decrease and thirteen patients with SVTs were remarkably improved only 5 minutes after infusion of DEXm (0.5-1 µg/kg), and SVTs of all patients without recurrence of SVTs in group D were eventually controlled and returned to normal sinus rhythm (NSR) by continuous intravenous infusion of DEXm for 10-minutes, which may be because DEXm can alter the ability to induce the arrhythmia by reducing sympathetic tension. Chrysostomou C et al. [17] also demonstrated that the continuous infusion of DEX during cardiac surgery can decrease incidence of postoperative ventricular and supraventricular tachyarrhythmias in pediatric patients. Meanwhile, none of patients developed clinically significant bradycardia, hypotension, respiratory depression, anoxia, and hemodynamic disorder, except for three patients developing mild hypotension in group D, which is perhaps due to use DEXm alone, and thus a synergistic or additive effect with other sedative and analgesic drugs is impossible. Furthermore, DEXm simultaneously maintain a sufficient level of sedation with a unique property of easy arousal. Previous studies indicated that DEXm can prevent shivering, which effectively reduce body oxygen consumption. Furthermore, the earliest recurrence of SVTs after infusion DEXm was 1 hour, and the duration of its effect increase the amount of arrhythmia-free time and hemodynamic stability [9]. Although DEXm caused mild hypotension, this limitation may be offset because of its unique minimal effect on respiration. Moreover, DEXm has bronchodilatory properties, therefore, it can still be used during asthma attacks. However, only two patients are eventually improved, other patients failed to respond in group M. The sedation degree in group M was deeper than group D (Table 3), and midazolam caused three patients SpO2 drop at T2 (>92%, Table 4), which got better after oxygen inhalation. Earlier studies have shown that intravenous infusion of midazolam 5 mg did not alter the reentrant tachycardia [3]. These data indicated that the sedation is not the mechanism of DEXm for the treatment of SVTs.
Patients suffer from hypokalemia, and/or diabetes, and/or hypertension, and/or coronary heart disease in our study (Table 2). These evidences demonstrated that DEXm had therapeutic effects on SVTs patients coupling with different diseases. It was impressive with a significantly (100%) termination of SVTs using DEXm, which may be associated with types of SVTs we chose. The types of SVTs have narrow-complex regular tachycardias and similar characteristics [18, 19]. Meanwhile, Delwadia S et al. [13] reported DEXm successfully treat SVTs in a 5 year-old boy with repair of atrial-septal-defect. In especial, DEXm does not cause any significant sinus pause or asystole. It has no negative inotropic or protachyarrhythmic effects, in contrast with many other agents such as β-adrenergic antagonists and amiodarone. Above all, compared with other drugs to treat SVTs, DEXm has a dual purpose: it can be used both as an anti-stress, sedative, analgesic and as an antiarrhythmic drug, which may be more suitable for surgical patient with SVTs.
Table 4 and Fig. 1 have shown that the rhythm or heart rate was significantly decreased, and SVTs were successfully terminated and converted to NSR using DEXm in adults. This is perhaps because DEXm can act on the medullary vasomotor center leading to decrease of catecholamine release from the nerve terminal. In addition, DEXm can decrease approximately 70% of epinephrine and norepinephrine levels in plasma, using the clinical recommended dosage [20]. Previous study reported that DEXm had therapeutic effect on atrial and junctional tachyarrhythmias [7], and can significantly decrease heart rate via regulating autonomic nerve homeostasis [21]. Figure 2-Figure 5 showed four patients with typical SVTs converted to NRS during 4–18 minutes after infusion DEXm. The key physiologic effects of DEXm can significantly affect the cardiac electrophysiology and conduction system, and thus depress sinus and atrioventricular (AV) nodal function [22, 23], as evidenced by significant prolongation of heart rate-adjusted PR and QT interval, AV node block cycle; lengthening of sinus node recovery time and effective refractory period [24]; diminishing atrial excitability [25].
HRV including HF, LF, and LF/HF is considered to be a quantitative indicator of autonomic nerve activity in the heart. HF and LF mainly reflects vagus nerve activity and sympathetic nerve activity, respectively [26]. LFnorm and HFnorm are the normalized values of LF and HF, respectively, consequently, which can more directly reflect the changes of sympathetic and vagus nerve regulation than LF or HF [27]. In our study, Fig. 6 has shown that HFnorm was elevated, and LFnorm and LF/HF were decreased after twenty patients infused DEXm in group D, which revealed that DEXm changed the balance between the sympathetic and parasympathetic tone, and regulated cardiac autonomic nervous system, and powerfully enhanced vagal neural activity, thereby overall rhythm or heart rate control was achieved. Finally, SVTs of all patient were successfully terminated, and converted to NSR. Above all, DEXm exerts antiarrhythmic effects by acting on peripheral and central nervous system. Some studies have shown that paroxysmal SVTs has an imbalance of autonomic nervous system, and tachyarrhythmia is treated by stimulating the vagus nerve and regulating the activity of autonomic nerve [28, 29]. Kamibayashi T et al. [21] by animal-dogs study demonstrated that the antiarrhythmic effects of DEXm are mediated through enhancement of the vagal neural activity. Previous studies have suggested that injury to cardiac parasympathetic nerves resulted in predominance of sympathetic activity during thoracic surgery, which was the primary autonomic mechanism triggering postoperative SVTs. Meanwhile, DEXm containing an imidazole ring can activate imidazoline receptors in the central nervous system, which can prevent adrenaline-induced ventricular tachycardia [30]. Hultin M et al. [31] reported that two patients (1.5 and 3.5 years) with recurrent SVTs were successfully treated by the intranasal administration of DEXm. In a word, DEXm with multiple administrations is safety, appropriate and effective for SVTs and may be an ideal agent for SVTs.
Additionally, use of DEXm can avoid other antiarrhythmic drugs, such as adenosine, verapamil and diltiazem, coupling with cardiac arrest, ventricular dysfunction and cardiovascular collapse [9], which showed DEXm had the important clinical value for surgical patient with SVTs. Therefore, it can be used relatively safely for patients with SVTs in usual clinical doses. However, large doses or rapid infusion DEXm should be used with caution. Because it can potentially have an adverse impact on patients with underlying heart disease, and thus may cause left ventricular dysfunction and hemodynamic instability [32]. Flores-González et al. [33] reported that the infusion duration of DEXm for 10 days and cessation it for 12 hours resulted in 4-year-old girl occurrence of a paroxysmal SVTs.