Rebound hyperkalemia in a dog with albuterol toxicosis after cessation of potassium supplementation.

OBJECTIVE: To describe the presentation of rebound hyperkalemia as a delayed side effect of albuterol toxicity in a dog. CASE SUMMARY: A 3-year-old female neutered mixed-breed dog was presented for albuterol toxicosis that led to a severe hypokalemia, hyperlactatemia, and hyperglycemia. The dog also experienced sinus tachycardia and generalized weakness. Treatment was instituted with intravenous fluid therapy and potassium supplementation, and the dog was monitored with a continuous electrocardiogram. Resolution of hypokalemia was documented 12 hours after initial presentation, at which time fluid therapy and potassium supplementation were discontinued. There were no further periods of sinus tachycardia, but instead the dog developed ventricular ectopy with rapid couplets (instantaneous rates of 300/min). An echocardiogram revealed normal cardiac size and function. Twenty-four hours after presentation, the patient developed severe hyperkalemia, despite discontinuation of fluids and potassium supplementation for 12 hours. Serial venous and urinary electrolytes were performed for determination of the fractional excretion of electrolytes. These data confirmed rebound hyperkalemia (7.0 mmol/L), consistent with a markedly increased fractional excretion of potassium, and secondary to the release of potassium from inside the cells. Fluid therapy with dextrose supplementation was provided until 36 hours postpresentation. The hyperkalemia resolved, and the dog was discharged after 44 hours of hospitalization. NEW OR UNIQUE INFORMATION PROVIDED: This case documents rebound hyperkalemia following treatment of albuterol toxicosis in a dog. This case highlights the importance of understanding the distribution of total body potassium when treating serum hypokalemia. Transcellular shifts of potassium, as in the case of albuterol toxicosis, can lead to rebound hyperkalemia even after discontinuation of potassium supplementation. This case further explores the utility of fractional excretion of electrolytes in elucidating the etiology and management of electrolyte disturbances.

Ablation of Inappropriate Sinus Tachycardia: A Systematic Review of the Literature.

OBJECTIVES: The goal of this study was to describe short- and long-term outcomes in all patients referred for inappropriate sinus tachycardia ablation, along with the potential complications of the intervention. BACKGROUND: Sinus node (SN) ablation/modification has been proposed for patients refractory to pharmacological therapy. However, available data derive from limited series. METHODS: The electronic databases MEDLINE, Embase, CINAHL, Cochrane, and Scopus were systematically searched (January 1, 1995-December 31, 2015). Studies were screened according to predefined inclusion and exclusion criteria. RESULTS: A total of 153 patients were included. Their mean age was 35.18 ± 10.02 years, and 139 (90.8%) were female. All patients had failed to respond to maximum tolerated doses of pharmacological therapy (3.5 ± 2.4 drugs). Mean baseline heart rates averaged 101.3 ± 16.4 beats/min according to electrocardiography and 104.5 ± 13.5 beats/min according to 24-h Holter monitoring. Two electrophysiological strategies were used, SN ablation and SN modification, with the latter being used more. Procedural acute success (using variably defined pre-determined endpoints) was 88.9%. Consistently, all groups reported high-output pacing from the ablation catheter to confirm absence of phrenic nerve stimulation before radiofrequency delivery. Need of pericardial access varied between 0% and 76.9%. Thirteen patients (8.5%) experienced severe procedural complications, and 15 patients (9.8%) required implantation of a pacemaker. At a mean follow-up interval of 28.1 ± 12.6 months, 86.4% of patients demonstrated successful outcomes. The symptomatic recurrence rate was 19.6%, and 29.8% of patients continued to receive antiarrhythmic drug therapy after procedural intervention. CONCLUSIONS: Inappropriate sinus tachycardia ablation/modification achieves acute success in the vast majority of patients. Complications are fairly common and diverse. However, symptomatic relief decreases substantially over longer follow-up periods, with a corresponding high recurrence rate.

Ivabradine in combination with metoprolol succinate in the treatment of inappropriate sinus tachycardia.

BACKGROUND: Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or a disproportional increase in HR during exercise. ß-blocker or calcium channel-blocker therapy is often noneffective or not well tolerated. The HR reduction on ivabradine is similar to ß-blockers but in some patients its efficacy to resolve all IST-related symptoms is limited. The aim of the study was to assess the efficacy and safety of combining ivabradine with metoprolol succinate in patients with refractory highly symptomatic IST. METHODS: Twenty patients (36 ± 10 years; 16 women) with IST were enrolled. All patients received metoprolol succinate 95 mg single dose during the first month of the study. After 4 weeks of treatment with metoprolol, ivabradine was administered as adjuvant therapy up to 7.5 mg twice daily. Holter monitoring and treadmill stress test were performed at baseline, after 4, and 8 weeks of the study, respectively. RESULTS: We observed significant and similar reduction in resting HR both for metoprolol and for combined therapy compared to the baseline. The mean HR during daily activity was significantly lower on ivabradine and metoprolol compared to monotherapy with ß-blocker. The combined treatment yielded a significant increase in exercise capacity as assessed by treadmill stress test. After 4 weeks of combined therapy a significant reduction in IST-related symptoms, measured by means of the European Heart Rhythm Association score, was observed. CONCLUSION: Combining ivabradine with metoprolol is an effective and well-tolerated treatment option for IST in patients with refractory to monotherapy.

Cardiac responses to the intrapericardial delivery of metoprolol: targeted delivery compared to intravenous administration.

Anti-arrhythmic drugs have narrow therapeutic ranges and typically can engender harmful side effects. The intrapericardial (IP) delivery of anti-arrhythmic agents proposes to achieve higher myocardial levels while minimizing plasma concentrations, thus diminishing systemic side effects. Furthermore, IP delivery enables concentrations at the target site to be more precisely controlled. Our study objective was to compare the relative cardiac effects of intrapericardial administration of metoprolol to standard intravenous (IV) delivery in a swine surgical model. In order to answer the question of how IP metoprolol affects sinus tachycardia, atrial electrophysiology, and pharmacokinetics compared with IV delivery, a medial sternotomy was performed on 21 swine that were divided into three groups: (1) After inducing sinus tachycardia, metoprolol boluses were delivered IP (n = 4) or IV (n = 4); (2) metoprolol was administered either IP (n = 3) or IV (n = 3) with saline controls (n = 3), and electrophysiologic data were collected; (3) metoprolol levels were tracked both in the blood (IV, n = 2) and pericardial (IP, n = 2) fluid. After either IP or IV delivery of metoprolol, heart rates were lowered significantly to 70% and 73% of control rate, respectively. The therapeutic effect of IV-administered metoprolol was considerably reduced after 1 h but was sustained longer in the IP group. Additionally, ventricular contractility and mean arterial pressure parameters were significantly lower in IV-treated animals but were nearly unaffected in IP-treated animals. With IP administration, the elimination half-life of metoprolol in pericardial fluid was 14.4 min with negligible accumulations in the plasma, whereas with IV delivery, the elimination half-life in plasma was 11.1 min with negligible amounts found in the pericardial fluid. The targeted intrapericardial delivery of metoprolol effectively lowers heart rates for sustained periods of time, with minimal effect on either ventricular contractility or mean arterial pressure. We did not observe dramatic changes in induced atrial fibrillation times or refractory periods using this model.

Efficacy of ivabradine administration in patients affected by inappropriate sinus tachycardia.

BACKGROUND: Inappropriate sinus tachycardia (IST) is characterized by an elevated heart rate (HR) at rest and an exaggerated HR response to physical activity or emotional stress. Beta-blockers and calcium channel blockers are the first-line therapy but sometimes are poorly tolerated due to side effects. OBJECTIVE: The purpose of this study was to evaluate the efficacy and safety of ivabradine, a selective inhibitor of the I(f) current of the sinoatrial node, in patients affected by IST. METHODS: Eighteen consecutive symptomatic patients (2 men and 16 women; mean age 45 +/- 15 years) affected by IST were enrolled in the study. Every patient underwent resting ECG, 24-hour Holter ECG, and exercise ECG at baseline and at 3-month and 6-month follow-up. RESULTS: Sixteen patients (14 women; mean age 41 +/- 14 years) completed the study. Holter ECG assessment showed a significant reduction of medium HR (P <.001) and maximal HR (P <.001, basal vs 3-6 months; P = .02, 3 vs 6 months). Minimal HR slightly decreased at 3 months and then stabilized (P = .49, 3 vs 6 months) despite an increased drug dose. Stress test showed a significant decrease at rest (P <.001) and maximal HR (P <.05), suggesting an increased tolerance to physical stress, which was confirmed by a progressive increase of maximal load reached (>100 W) during stress test at 3 months (75%) and 6 months (85%). One patient was excluded because of phosphenes despite dose lowering, and another patient did not complete the protocol. CONCLUSION: Ivabradine could represent an effective and safe alternative to calcium channel blockers and beta-blockers for treatment of IST.

Impaired negative chronotropic response to adenosine in patients with inappropriate sinus tachycardia.

INTRODUCTION: Adenosine is an endogenous nucleoside that has an important role in the diagnosis and treatment of several cardiac arrhythmias. However, its effects on inappropriate sinus tachycardia (IST) are not well established. METHODS AND RESULTS: In this study, the response to intravenous adenosine (0.1 to 0.15 mg/kg) was studied in 18 patients (age 46+/-15 years) with IST. In a subset of patients (n = 5), the direct effects of adenosine were assessed during pharmacologic beta-adrenergic and cholinergic blockade. Atrial cycle length (ACL) was measured before adenosine injection, at the time of the greatest cycle length prolongation, and during the maximum rebound acceleration of heart rate. Eighteen subjects (age 46+/-11 years) with normal sinus rhythm undergoing clinically indicated electrophysiologic study served as controls. Adenosine did not terminate IST in any patient. The maximum dose of adenosine prolonged the sinus interval significantly, from 780+/-128 msec to 985+/-225 msec (P < 0.001) in the control subjects. In contrast, adenosine caused no significant lengthening of atrial cycle length (527+/-69 msec vs 590+/-148 msec; P = NS) in the patients with IST. Similar difference in the response to adenosine was seen during the pharmacologic autonomic blockade. The reflex increase of the sinus rate (rebound effect) was greater in the control subjects than in the patients with IST (21.2%+/-9.7% vs 8.5%+/-8.8%; P < 0.001). CONCLUSION: The usual negative chronotropic effect of adenosine was impaired in the patients with IST. This may have important diagnostic implications and provide new insight into the mechanism(s) of IST.

Three-dimensional nonfluoroscopic mapping and ablation of inappropriate sinus tachycardia. Procedural strategies and long-term outcome.

OBJECTIVES: We conducted this study to assess long-term results of three-dimensional (3-D) mapping-guided radiofrequency ablation (RFA) of inappropriate sinus tachycardia (IST). Change in activation after the administration of esmolol was also assessed and compared to the shift documented with successful sinus node (SN) modification. BACKGROUND: The long-term results after RFA of IST have been reported to vary between 27% and 66%. METHODS: Thirty-nine patients (35 women, mean age 31 +/- 9 years) with debilitating IST were included in the study. The area around the earliest site of activation recorded using the 3-D mapping system was targeted for ablation. The shift in the earliest activation site after administration of esmolol was compared with the shift after RFA. RESULTS: The heart rate at rest and in drug-free state ranged between 95 and 125 beats/min (mean 99 +/- 14 beats/min). Sinus node was successfully modified in all patients. Following ablation, the mean heart rate dropped to 72 +/- 8 beats/min, p < 0.01. The extent of the 3-D shift in caudal activation along the crista terminalis was more pronounced after RFA than during esmolol administration (23 +/- 11 mm vs. 7 +/- 5 mm, respectively, p < 0.05). No patient required pacemaker implantation after a mean follow-up time of 32 +/- 9 months; 21% of patients experienced recurrence of IST and were successfully re-ablated. CONCLUSIONS: Three-dimensional electroanatomical mapping seems to facilitate and improve the ablation results of IST. The difference in caudal shift seen after esmolol administration and following SN modification suggests that adrenergic hypersensitivity is not the only mechanism responsible for the inappropriate behavior of the SN.