The use of dexmedetomidine continuous rate infusion for horses undergoing transvenous electrical cardioversion — A case series

Abstract

Five horses were presented for treatment of atrial fibrillation by transvenous electrical cardioversion (TVEC). A dexmedetomidine infusion was administered for sedation during positioning of the cardioversion catheters, and continued during general anesthesia. Shocks were applied until return to sinus rhythm. Dexmedetomidine infusion provided excellent conditions for TVEC catheter placement and procedure.

A trial fibrillation is one of the most common pathologic cardiac arrhythmias diagnosed in horses and significantly impairs performance capacity. Medical treatment with quinidine can be attempted in these cases, but transvenous electrical cardioversion (TVEC) is becoming more popular as an alternative treatment, considering the frequent adverse effects of quinidine and the high success rate of TVEC (1). Despite becoming a more frequent procedure, there are only a few reports of the anesthetic management of these cases (2–4).

Dexmedetomidine is an α-2 adrenoreceptor agonist that is gaining interest as part of a balanced anesthetic protocol in equine anesthesia (5–7) as it provides reliable sedation, has a minimum alveolar concentration (MAC) sparing effect, and potentially results in better quality of recovery compared to other balanced protocols used in horses (8,9). Its potential cardioprotective (10,11) and anti-arrhythmic properties (12,13) make it a potentially suitable drug to use as a part of the anesthetic protocol in horses presented for TVEC.

This case series describes the use of a dexmedetomidine constant rate infusion for sedation during instrumentation and as part of a balanced anesthetic protocol for horses undergoing a TVEC procedure for treatment of atrial fibrillation.

Case descriptions

Atrial fibrillation was diagnosed in 3 Warmblood, 1 Shire, and 1 Trakehner horses (Table 1) referred to the Equine Department of the Vetsuisse Faculty, University of Zurich for exploration of poor performance or arrhythmia. The horses were used for pleasure riding, breeding, dressage, or jumping. The exact duration of atrial fibrillation was not known but was estimated to be of at least 1 mo (horse 3) or 4 mo (remaining horses) based upon the medical history. None of the horses had been treated for atrial fibrillation. After a full physical examination, complete blood cell count, serum biochemistry profile including cardiac troponin I concentration (cTnI), and a complete cardiac examination including electrocardiography and echocardiography, the horses underwent a TVEC procedure for treatment of atrial fibrillation.

Table 1.

General information and echocardiographic findings at admission

Horse	Breed	Age (years)	Gender	Body weight (kg)	Resting heart rate (bpm)	Cardiac troponin I (ng/mL)	Echocardiography
1	Shire	12	Female	760	28	0	Trace of tricuspid and aortic regurgitation
2	Warmblood	10	Male, castrated	660	35	0	Mild aortic and trivial pulmonary regurgitation
3	Trakehner	10	Male, castrated	655	40	0.12	Moderate mitral and aortic regurgitation
4	Warmblood	9	Female	580	34	NA	Trivial mitral, tricuspid, aortic, and pulmonary regurgitation
5	Warmblood	13	Male, castrated	620	26		Mild mitral regurgitation, moderate and progressive left atrial dilation, progressive left ventricular dilation

bpm — beats per minute. NA — Not available.

The signalment and echocardiographic findings for the horses at admission are summarized in Table 1. The horses were fasted for 12 h before the procedure, but water was provided free choice all the time. In the morning of the procedure, all horses received flunixine (Flunixin ad us. vet; Biokema SA, Crissier, Switzerland), 1 mg/kg body weight (BW), IV, sodium penicillin (Penicilline Natrium Streuli; G. Streuli & Co AG, Uznach, Switzerland), 30 000 IU/kg BW, IV, and gentamicin (Genta; CP-Pharma GMBH, Burgdorf, Germany), 9 mg/kg BW, IV, through a previously placed left jugular vein catheter. A bolus dose of dexmedetomidine (Dexdomitor; Janssen Animal Health, Germany), 3.5 μg/kg BW, was prepared in 20 mL of NaCl (NaCl; Fresenius Kabi AG, Switzerland). A dose of 1.75 μg/kg BW, was administered together with butorphanol (Alvegesic 1% forte ad us. vet.; Virbac AG, Glattbrugg, Switzerland), 30 μg/kg BW, slowly intravenously in the box, and then the horses were walked to the procedure room where the remaining dexmedetomidine, 1.75 μg/kg BW, was administered. When the sedation was considered insufficient, additional boluses of 0.5 to 2 μg/kg BW dexmedetomidine were administered to effect (horses 1, 2, 4).

The TVEC procedure was performed in a manner similar to a previously described method (13). However, in contrast to that method, percutaneous catheter introducers (8.5 French; Argon Medical Devices, Athens, Texas, USA) were used for placement of the cardioversion catheters. Catheters were placed with horses standing free in the room, restrained by an experienced handler. To provide a constant level of sedation during the placement of the cardioversion catheters, a continuous rate infusion (CRI) of dexmedetomidine was started at a dose of 1.75 μg/kg BW per hour administered with an infusion pump (Phoenix D; Schoch Electronics AG, Möriken, Switzerland), when an adequate initial sedation was reached in the procedure room. The quality of sedation was assessed by the same experienced anesthetist (RB) in all horses. The criteria that were assessed were head and ear position, head and ear movement in response to external stimuli, and catheter placement, and movement. Sedation was considered adequate when the horse was standing still, had a low head position with drooping ears and lip, and did not react to external stimulation. When required, additional sedation was provided by administering dexmedetomidine boluses, with a dose ranging from 0.5 to 2 μg/kg BW and the rate of the CRI adapted subsequently. Details of the anesthetic drugs and doses used are presented in Table 2. The total dose rates for dexmedetomidine during sedation were calculated by determining the total amount of dexmedetomidine administered as CRI and additional boluses, and dividing it by the total duration of the sedation phase. Placement of the cardioversion catheter was pressure-guided and correct positioning of the catheters in the right atrium and in the left branch of the pulmonary artery was confirmed by echocardiography and thoracic radiography. In contrast to the original description of the procedure (13), thoracic radiographs were obtained before inducing anesthesia.

Table 2.

Drug doses administered as a part of the anesthetic protocol for 5 horses treated for atrial fibrillation by transvenous electrical cardioversion, number of shocks required, cardioversion energy, and outcome

Horse	Sedation	DEX CRI total rate (μg/kg per hour)	Duration of sedation (min)	Dexmedetomidine CRI rate intraoperatively (μg/kg per hour)	Post anesthetic sedation	Number of shocks	Cardioversion energy (J)	Immediate outcome	Cardiac troponin I 6 h post conversion (ng/mL)	Cardiac troponin I 24 h post conversion (ng/mL)	2-year follow-up
1	DEX 10 μg/kg Butorphanol 30 μg/kg	5	120	5.3	DEX 3 μg/kg IV	8	275	NSR	0.22	0.01	NSR
2	DEX 4.5 μg/kg Butorphanol 30 μg/kg	10	75	2.3	DEX 1 μg/kg IV	7	250	NSR	0.00	0.03	NSR
3	DEX 3.5 μg/kg Butorphanol 30 μg/kg	10.4	80	2.3	DEX 1 μg/kg IV	8	275	NSR	0.04	0.01	Loss of follow-up
4	DEX 5.5 μg/kg Butorphanol 30 μg/kg	6.7	90	2.2	DEX 1 μg/kg IV	7	250	NSR	0.00	0.01	NSR
5	DEX 3.5 μg/kg Butorphanol 30 μg/kg	9.2	75	1.75	DEX 1 μg/kg IV	6	225	NSR	0.16	0.14	Died 48 h after procedure

DEX — dexmedetomidine; NSR — normal sinus rhythm.

The catheters were then secured in place, and anesthesia was induced in the same room with ketamine (Narketan; Chassot AG, Basel, Switzerland), 2.2 mg/kg BW, and diazepam (Valium; Roche Pharma, Basel, Switzerland), 0.02 mg/kg BW, IV. After orotracheal intubation with a cuffed endotracheal tube (internal diameter 26 or 30 mm), the horses were positioned on an air mattress in left lateral recumbency and a urinary catheter was inserted. The endotracheal tube was connected to a large animal rebreathing unit (LAVC-2000; JD Medical distributing, Phoenix, Arizona, USA) with an out-of-circuit isoflurane vaporizer. Anesthesia was maintained with isoflurane (Isoflo ad us. vet.; Dr. Graeub AG, Bern, Switzerland) in oxygen and air (FiO₂: 0.5). Isoflurane was given to effect in order to maintain a sluggish palpebral reflex. Lactated Ringer’s solution (Ringer-Lactat-Lösung; Fresenius Kabi AG) was delivered at a rate of 5 mL/kg BW per hour. The dexmedetomidine CRI was maintained, and the rate was chosen based on individual rate necessary to maintain an adequate sedation for cardioversion catheter placement (1.75 to 5.3 μg/kg BW per hour; Table 2). Controlled mechanical ventilation was started for each horse with a tidal volume ranging from 6 to 10 mL/kg BW and the respiratory rate was adapted in order to maintain P_E CO₂ between 4.5 and 5.8 kPa (35 to 45 mmHg). Monitoring consisted of electrocardiogram, pulse oximetry, capnography, measurement of inhaled and exhaled gas composition, and invasive blood pressure monitoring (Cardiocap S5; Datex Anandic Medical, Schaffhausen, Switzerland). For invasive blood pressure monitoring, a 22-gauge catheter was placed in the right transverse facial artery and connected to a pressure transducer placed at the level of the manubrium, and zeroed at atmospheric pressure. One arterial blood gas was analyzed (iStat; AxonLab AG, Baden, Switzerland) at least 5 min before the first shock was applied. Dobutamine (Dobutrex; Eli Lilly S.A., Switzerland) was started a rate of 0.5 μg/kg BW per min and the rate was adapted until the horse had a stable mean arterial blood pressure > 65 mmHg. The Dobutamine CRI was stopped at least 5 min before the first shock was applied. The vital parameters, arterial blood gas results and total dobutamine doses are presented in Table 3.

Table 3.

Mean and ranges of monitored variables for 5 horses treated for atrial fibrillation, during general anesthesia for transvenous electrical cardioversion. The dobutamine dose is calculated by dividing the total amount of dobutamine received over the entire anesthesia time

Horse	Heart rate (bpm)	Repiratory rate (breaths/min)	ETIso (%)	Mean arterial pressure (mmHg)	pH	paCO2 (mmHg)	paO2 (mmHg)	BE (mEq/L)	Dobutamine (μg/kg per minute)	Duration of anesthesia (min)
1	33 (31 to 36)	6.5 (6 to 7)	1.1 (1.0 to 1.2)	87 (81 to 91)	7.4	48	129	7	0.12	55
2	38 (31 to 49)	5.9 (5 to 6)	1.1 (1.1 to 1.3)	87 (73 to 99)	7.47	38.7	83	1	0.05	50
3	35 (28 to 41)	6.1 (6 to 7)	0.9 (0.7 to 1.3)	102 (94 to 118)	7.41	38.4	124	0	0.03	40
4	28 (24 to 36)	6 (4 to 7)	1.2 (1.1 to 1.3)	66 (60 to 76)	7.40	42.5	138	2	0.12	45
5	39 (31 to 49)	5.7 (3 to 9)	1.0 (0.7 to 1.2)	86 (74 to 99)	7.37	46.8	181	2	0	45

bpm — beats per minute; ET_Iso — end-tidal isoflurane; p_aCO₂ — partial pressure of CO₂ in arterial blood; p_aO₂ — partial pressure of oxygen in arterial blood; BE — base excess.

The TVEC protocol started with a first shock of 100 J and increased in increments of 25 J. The horses required between 6 and 8 shocks to convert to normal sinus rhythm. Mean arterial blood pressures were maintained, except in 2 horses where pressures dropped by 15 mmHg during and after application of the shocks. Anesthesia was maintained for another 20 min during which ECG was observed for immediate recurrence of atrial fibrillation, and morphine, 0.1 mg/kg BW, IM was administered. The TVEC catheters and the catheter introducers were removed and the horses were hoisted into a padded recovery stall, adjoining the procedure room. Post-anesthetic sedation consisted of intravenous dexmedetomidine, 1 μg/kg BW for all horses except horse 1, which had exhibited a difficult behavior prior to anesthesia and received a dose of 3 μg/kg BW. The trachea was extubated after 20 min or when a swallowing reflex was observed. Recoveries were uneventful in all horses and the horses were standing between 32 and 47 min after being placed in the recovery box; horses had a recovery score of 1 to 2 of 5. Cardiac troponin I concentrations were measured 6 and 24 h after cardioversion (Table 2; normal < 0.06 ng/mL; 14). Echocardiography and 24-hour Holter ECG monitoring were conducted 1 day and 3 days after successful cardioversion, followed by re-evaluation or telephonic follow-up at regular intervals.

In horse 5, progressive left atrial and left ventricular dilation, occurrence of supraventricular premature beats (13 over 24 h) and large numbers of ventricular premature beats (173 single and 5 couplets over 24 h) over the first day of follow-up after TVEC prompted for treatment with Sotalol (Sotalex 80 mg; Bristol-Myers Squibb, Steinhausen, Switzerland), 1 mg/kg BW, PO, q12h, and Quinapril (Accupro 20 mg; Pfizer, Zürich, Switzerland), 0.25 mg/kg BW, PO, q24h. On day 2 after the TVEC procedure, the horse developed progressive ventricular arrhythmias and clinical signs of dyspnea, pulmonary edema, and restlessness. Intravenous treatment with furosemide, lidocaine, and magnesium sulfate was unsuccessful and the horse died from progressive multiform ventricular arrhythmias. Postmortem examination revealed moderate mitral valve endocardiosis, multifocal endocardial and myocardial fibrosis in the left atrium, multiple endocardial tears in the left atrium and ventricle, and moderate to severe subacute diffuse pulmonary congestion. The cardiac arrhythmias and death may have been the result of the underlying structural cardiac disease; however, an influence of the TVEC procedure cannot be ruled out. Of the remaining horses, 3 were still in normal sinus rhythm 2 y after the procedure and 1 horse was sold and lost to follow-up.

Discussion

Although atrial fibrillation is one of the most frequent pathologic cardiac arrhythmias in the horse and its treatment with TVEC is becoming more and more popular, there are only few reports in the literature on the anesthetic management for this procedure. The present case series reports a new safe standing sedation protocol and anesthetic maintenance including dexmedetomdine CRI and inhalational anesthesia with isoflurane, resulting in stable cardiopulmonary function and good quality recovery.

In the normal horse, ventricular filling is dependent on the duration of diastole to maintain cardiac output, as it largely depends on passive blood flow from the venous circulation during rapid, early-diastolic ventricular filling. Late-diastolic atrial contraction further contributes to ventricular filling and accounts for 15% to 25% of cardiac output at rest (16). During atrial fibrillation, the uncoordinated depolarization of the atrial myocardial cells results in the absence of an atrial contraction. This can be detrimental to cardiac output, particularly during exercise when heart rates are high, diastole is short and atrial contribution to ventricular filling is crucial to maintain an adequate ventricular preload. High heart rates should generally be avoided in these patients (17).

Transvenous electrical cardioversion consists of the administration of an electrical shock across the atria in order to terminate disorganized electrical activity and restore normal sinus rhythm. There is evidence that this procedure produces cardiomyocyte damage, as can be detected by increased plasma concentrations of cardiac troponins (18).

Dexmedetomidine has a myocardial energy sparing effect at low doses, and at increasing doses, maintains the balance between myocardial oxygen demand and delivery due to its effects on the cardiac α-2 receptors (10). In patients with heart disease and possible myocardial injury, these effects may be beneficial. By producing α-2 mediated coronary vasoconstriction, dexmedetomidine helps to favor redistribution of blood flow into ischemic regions of the myocardium (19,20). The effect of TVEC on equine myocardium is not described, but the electric shock applied directly to the myocardium may cause a degree of ischemia. The reduction in heart rate produced by dexmedetomidine also favors myocardial perfusion and therefore oxygen delivery by increasing the time available for coronary blood flow. In isolated rat hearts, dexmedetomidine has a cardioprotective, likely dose-dependent effect on global ischemia (11), but administration of dexmedetomidine in that context must take place before the onset of myocardial injury. The use of dexmedetomidine in horses with atrial fibrillation that undergo TVEC procedure may therefore have beneficial effects, as it might increase the tolerance to potential ischemic injuries during general anesthesia. In this respect, the high affinity for the α-2: adrenoreceptors in comparison to other non-specific α-2 adrenoreceptor agonists such as xylazine, detomidine, or romifidine could be of benefit. Its use as a CRI during instrumentation might be further advantageous, since it provides stable and adequate plasma concentrations prior to general anesthesia and the TVEC procedure, hence before potential myocardial injury might occur. In the horses in this report, myocardial damage was likely minimal, since plasma cardiac troponin I concentrations were only mildly elevated 6 h after the procedure in 2 horses and 24 h after the procedure in 1 horse. Cardiac troponin I concentrations were lower than previously described after TVEC by another group (18).

For TVEC in horses, the placement of cardioversion catheters is done in the standing position which allows an easier catheter placement and reduces time in general anesthesia. In this study, catheter placement took between 75 and 120 min. Deep sedation is required, as the horses should not move during catheter placement and anesthesia should be induced without delay once the catheters are in place. The most reliable drugs used for sedation in horses are α-2 adrenoreceptor agonists in combination with opioids. Butorphanol, the opioid used in our cases, has no significant influence on cardiopulmonary function (21) but provides some analgesia and increases reliability of sedation. Use of α-2 adrenoreceptor agonists following bolus administration, however, will cause vasoconstriction through peripheral action on α-2 adrenoreceptors, followed by a baroreceptor reflex-induced decrease in heart rate. They also have a central effect on α-2 adrenoreceptors that causes sedation, analgesia, and a decrease in sympathetic output. The cardiovascular effects depend on the drug and the dose used (5,22–24).

For prolonged standing sedation, the use of a CRI is preferable to repeated boluses. Constant rate infusion results in a constant level of sedation with stable plasma drug concentrations, while cardiovascular effects, which tend to be profound after a single bolus, tend to stabilize over time (25,26).

Of all α-2 adrenoreceptor agonists, dexmedetomidine is the one with greatest affinity for α-2 adrenoreceptors, limiting the undesirable cardiovascular α-1 effects, and promoting the sedation and analgesia. It has been studied under experimental (5) and clinical conditions (6,7) in horses. Its very short half-life after single bolus administration in comparison with other α-2 adrenoreceptor agonists (5,23,24) makes it suitable for use as a CRI, in which plasma concentrations and therefore depth of sedation can be adjusted rapidly to the patient’s needs. Dexmedetomidine also provides significant analgesia (23), produces MAC sparing effect, and improves the quality of recovery when used as part of a balanced anesthetic protocol (6,7).

Dexmedetomidine CRI dose rates have not been developed for prolonged sedation in horses, but published dose rates in horses leading to sedation and MAC reduction approximate 50% of the dose rates of medetomidine (6), which consists of 50% dexmedetomidine and 50% levomedetomidine, an enantiomer without significant action (27). Therefore it was expected that dexmedetomidine could be dosed following previously described medetomidine protocols (26), using half of the dose of medetomidine. However, the depth of sedation was adjusted to the patients’ needs, judged by an experienced anesthetist, and additional boluses were administered or infusion rates were adjusted as necessary to produce adequate sedation. This resulted in a large variability of loading doses and infusion rates, probably because of the variable temperaments of the horses. Due to the very short-lived effect of the dexmedetomidine, maintenance of adequate depth of sedation seemed more difficult in fractious horses than with other longer acting α-2 adrenoreceptors.

Transvenous electrical cardioversion of atrial fibrillation can profoundly affect cardiovascular function during general anesthesia. During TVEC, when electrical shocks are applied, cardiac output and blood pressure are unstable (3). Nonetheless, during anesthesia, oxygen delivery to the muscles should be maintained to ensure a safe recovery of anesthetized horses. Pretreatment with dexmedetomidine decreases the oxygen demand of the peripheral tissues and increases the tolerance of tissues to ischemic injuries despite a decrease in cardiac output (28). This can be an additional benefit of the use of dexmedetomidine during TVEC in horses.

In the horses presented here, dobutamine was used at very small doses to maintain a stable mean arterial blood pressure above 65 mmHg prior to application of the first electrical shock. It was stopped 5 min before the first shock to avoid potential proarrhythmic effects during the TVEC procedure. As the elimination half-life of dobutamine is about 2 min (29), its influence on cardioversion and subsequent blood pressures was expected to be minimal. Nonetheless, mean arterial blood pressures as well as heart rates stayed within an acceptable range throughout anesthesia. This was likely made possible by being able to decrease the isoflurane to levels below the reported MAC for horses, as a result of the addition of dexmedetomidine.

Dexmedetomidine in the present report proved to be useful, although individual necessary dose ranges were wide. Resulting sedation was good, analgesia appeared adequate, cardiopulmonary function during anesthesia was stable, and the quality of recovery was good. The influence of dexmedetomidine on the outcome of the TVEC has not been determined, but its cardio-protective and energy sparing effects on the myocardium and the peripheral tissues make it an interesting option as a part of the anesthetic protocol. CVJ