EPISODIC SYNCOPE CAUSED BY VENTRICULAR FLUTTER IN A TIGER (PANTHERA TIGRIS) Author(s): Daniel M. DeLillo , M.S., D.V.M., Sophy A. Jesty , D.V.M., Dipl. A.C.V.I.M. and Marcy J. Souza , D.V.M., M.P.H., Dipl. A.B.V.P. (Avian), Dipl. A.C.V.P.M. Source: Journal of Zoo and Wildlife Medicine, 44(2):500-504. 2013. Published By: American Association of Zoo Veterinarians DOI: http://dx.doi.org/10.1638/2012-0203.1 URL: http://www.bioone.org/doi/full/10.1638/2012-0203.1

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EPISODIC SYNCOPE CAUSED BY VENTRICULAR FLUTTER IN A TIGER (PANTHERA TIGRIS)

Daniel M. DeLillo, M.S., D.V.M., Sophy A. Jesty, D.V.M., Dipl. A.C.V.I.M., and Marcy J. Souza, D.V.M., M.P.H., Dipl. A.B.V.P. (Avian), Dipl. A.C.V.P.M.

Abstract: Acaptive, 9-yr-old castrated male tiger (Panthera tigris) from an exotic cat sanctuary and rescue facility was observed to have three collapsing episodes within a 2-wk interval prior to being examined by veterinarians. No improvement in clinical signs was noted after empiric treatment with phenobarbital. During a more complete workup for epilepsy, ventricular flutter was observed on electrocardiogram (ECG). The resolved with a single intravenous bolus of lidocaine. Cardiac structure and function were unremarkable on echocardiogram and cardiac troponin I levels were within normal limits for domestic felids. No significant abnormalities were noted on abdominal ultrasound. Complete blood count and biochemistry panel were unremarkable, and heartworm antigen and Blastomyces urine antigen enzyme-linked immunosorbent assays were negative. Antiarrhythmic treatment with sotalol was initiated. On follow-up ECG performed 1 mo later, no significant were noted, and clinical signs have completely resolved. Key words: Arrhythmia, collapse, Panthera tigris, syncope, tiger, ventricular flutter.

BRIEF COMMUNICATION and intermittent nature of the events. Also, seizures and syncope may coexist in the same The term ‘‘collapse’’ refers to a loss of postural patient, adding to the diagnostic complexity.1 tone with or without progression to recumbency During a cardiovascular-mediated syncopal and with or without loss of consciousness.7 event, an animal will usually collapse into lateral Causes for collapse can be broadly categorized recumbency and may display multifocal myoclo- as either syncopal or nonsyncopal. Syncope is defined as a sudden transient loss of conscious- nus, opisthotonos, vocalization, and urination. ness and postural tone with spontaneous recovery However, it is uncommon to see persistent facial that occurs as a result of hypoperfusion and lack spasms, persistent tonic/clonic motion, defeca- 6 of sufficient nutrient delivery (i.e., glucose) to the tion, postictal dementia, or neurologic deficits. reticular activating system and cerebral hemi- ‘‘Convulsive syncopal episodes’’ resulting from spheres of the brain for at least 6–8 sec.1,2,9,12 severe hypotension or are typically Causes for syncope include decreased cardiac preceded by loss of muscle tone, whereas seizure output from loss of preload, mechanical outflow activity is usually preceded by atypical limb or obstruction, and arrhythmias, loss of vascular facial movement or staring spells prior to the loss resistance, often by neurocardiogenic reflex mech- of body tone.6 anisms, and focal or generalized decrease in The most common causes for syncope in cerebral perfusion caused by cerebrovascular veterinary patients are cardiogenic in nature. disease.12 Nonsyncopal causes for collapse occur Rhythm disturbances secondary to inherent car- without alteration to cerebral blood flow and diac disease account for almost two-thirds of the include metabolic disturbances like hypoglycemia cases of syncope seen in dogs and cats.6 The or electrolyte disorders, neurologic abnormalities following brief communication is, to the authors’ like seizures or neuromuscular disease, and hyp- knowledge, the first case of arrhythmic syncope oxia.7,8,12 documented in a tiger. It is important to attempt to differentiate A captive, 9-yr-old castrated male tiger (Pan- syncopal from nonsyncopal causes of collapse; thera tigris) from an exotic cat sanctuary and differentiation is often difficult due to the many rescue facility was observed to have three col- possible etiologies, similar clinical presentations, lapsing episodes within a 2-wk interval prior to being examined by veterinarians. The events were suspected to be seizures based on the staff ’s From the Departments of Small Animal Clinical description of the episodes (collapse with exten- Services (DeLillo, Jesty) and Biomedical and Diagnostic Sciences (Souza), University of Tennessee Veterinary sor rigidity lasting approximately 7 to 8 sec with Medical Center, 2407 River Drive, Knoxville, Tennessee immediate recovery). After a second episode was 37996, USA. Correspondence should be directed to Dr. observed, the tiger was empirically treated with Jesty ([email protected]). phenobarbital (0.74 mg/kg p.o. b.i.d.; Qualitest

500 DELILLO ET AL.—VENTRICULAR FLUTTER IN A TIGER 501

Pharmaceuticals, Huntsville, Alabama 35811, laria immitis was negative but was weakly positive USA). When a third episode occurred after on antibody ELISA. antiepileptic treatment had been initiated, mag- Complete blood count and serum biochemistry netic resonance imaging (MRI) was advised to panels were unremarkable except for a mild look for a possible structural brain lesion. Prior to azotemia (blood urea nitrogen: 38 mg/dL; creat- these incidents, the tiger had no previously inine: 1.8 mg/dL). Urinalysis showed mild to reported medical issues and was in ideal body moderate proteinuria with adequate concentra- condition at the time of this brief communication tion (urine specific gravity: 1.052). No evidence of (174 kg). There was no known toxin exposure; Blastomyces was detected on urine antigen enzyme however, Blastomyces dermatitidis had been previ- immunoassay. Abdominal radiographs showed ously reported on the premises. mildly irregular kidney margins suggestive of The tiger was premedicated (5 mg midazolam chronic renal disease but were otherwise unre- i.m.; Hospira Inc., Lake Forest, Illinois 60045, markable. An abdominal ultrasound confirmed USA) and then immobilized (300 mg ketamine; that the kidneys were irregularly marginated and Bioniche Teoranta, Inveria County, Galloway, hyperechoic with mild loss of corticomedullary Ireland, 1.5 mg dexmedetomidine; Pfizer Animal distinction. The contents of the urinary bladder Health, New York, New York 10017, USA, and 5 were markedly echogenic, consistent with pro- mg midazolam i.m.). Adequate sedation for teinuria. The only other abnormality noted on intubation was not seen within 20 min, so abdominal ultrasound was mild thickening of the additional medication was administered (100 mg gall bladder wall. ketamine and 0.5 mg dexmedetomidine i.m.). The While positioning the animal for radiographs, a tiger was then maintained on 3% inhaled isoflur- small, 1-cm mass was discovered on the caudo- ane(Abbott,Chicago,Illinois60064,USA). medial aspect of the left forelimb. Aspirates of the During anesthetic preparation for MRI, parox- mass were submitted for cytology. The samples ysms of a sinusoidal arrhythmia were noted on the were of low cellularity and contained predomi- electrocardiogram (ECG) monitor. During these nantly individual spindle-shaped cells with mini- paroxysms, the heart was difficult to auscultate, mal anisocytosis and anisokaryosis, low numbers and femoral pulses were weak to absent. After of erythrocytes, and rare, poorly preserved mast verifying that all leads and equipment were cells. The findings were more suggestive of a properly attached and working so as to rule out benign, non-neoplastic, inflammatory lesion with artifact, a diagnostic six-lead ECG was obtained fibroblasts; however, the low numbers of mast to better characterize the rhythm. The ECG cells in the presence of spindle cells raised the showed a predominant sinus rhythm at a rate of index of suspicion for a mast cell tumor. It was approximately 80 bpm with frequent paroxysms decided that if the tiger needed to be anesthetized of ventricular flutter at a rate of approximately in the future, the mass would be removed and 250 bpm (Fig. 1A). A single bolus of lidocaine was submitted for histopathology; the period of anes- given (1.15 mg/kg i.v.; Hospira Inc.) and within 4 thesia that day had already been protracted and min, complete resolution of the arrhythmia was results from the fine-needle aspirate were not documented (Fig. 1B). Recurrence was not seen available until the tiger was already recovering over the next 4 hr, while the tiger’s workup was from anesthesia. completed. In light of the diagnostic findings, it was Transthoracic echocardiography was per- suspected that the reported collapsing episodes formed to look for structural cardiac causes for were syncopal episodes from the ventricular the arrhythmia. Subjective right and left ventric- flutter, rather than seizures. The tiger was placed ular dilation with mild to moderate systolic on sotalol as an antiarrhythmic medication (360 dysfunction was noted. These changes were mg p.o. b.i.d.; Qualitest Pharmaceuticals), and assumed to be anesthesia related and not signif- phenobarbital was discontinued. A surveillance icant enough to warrant treatment. No other camera was placed within the tiger’s enclosure, abnormalities were observed on echocardiogram. and no further syncope was observed over the Blood was submitted for cardiac troponin I levels following 2 mo. A month after the initial workup, to look for evidence of ongoing cardiomyocyte a repeat ECG was acquired under sedation (1.5 necrosis or strain but were within the normal mg dexmedetomidine and 10 mg midazolam i.m.). range for domestic felids (0.14 ng/ml; reference A physiologic sinus arrhythmia at a rate of range: 0.00–0.15 ng/ml). An antigen enzyme- approximately 40 bpm was observed during the linked immunosorbent assay (ELISA) for Dirofi- time of sedation (Fig. 1C). No significant arrhyth- 502 JOURNAL OF ZOO AND WILDLIFE MEDICINE

Figure 1. Six-lead ECGs acquired from the tiger. A. Note the sinusoidal waveform consistent with paroxysmal ventricular flutter at a rate of 250 bpm. The ventricular flutter terminates with a pause followed by normal P, QRS, and T morphology, consistent with normal sinus rhythm at a rate of 80 bpm. Paper speed: 50 mm/sec; amplitude: 10 mm/mV. B. After treatment with lidocaine, note the normal sinus rhythm at a rate of 70 bpm. Paper speed: 10 mm/sec; amplitude: 10 mm/mV. C. Follow-up six-lead ECG 1 mo after initiating treatment with sotalol showing normal sinus arrhythmia with a rate of 40 bpm. Paper speed: 50 mm/sec; amplitude: 10 mm/mV. DELILLO ET AL.—VENTRICULAR FLUTTER IN A TIGER 503 mias were present. At the time of this writing, the reasons, it is very likely that the tiger was tiger continues to do well and has remained experiencing syncopal episodes from paroxysmal asymptomatic on sotalol. ventricular flutter. To completely confirm or rule Ventricular flutter is a very rapid, monomorphic out that the arrhythmia was the cause of clinical ventricular in which the individual signs, an ambulatory ECG recording device, such waves and segments fuse into a sinusoidal pat- as a Holter monitor or implantable loop recorder, tern.5,10,13 Sustained ventricular flutter (typically wouldhavetohavebeeninplaceandrecording lasting greater than 30 sec) results in faintness, while an episode occurred. Such devices are not followed by loss of consciousness, seizures, apnea, practical in nondomesticated animals, so empiric and eventually, if persistent, death.5,10 Most pa- treatment is often the mainstay of therapy if a tients become hypotensive from inadequate ven- serious arrhythmia is documented in a collapsing tricular filling and subsequent poor cardiac animal. As no similar episodes were observed after output. The condition often degenerates into initiating antiarrhythmic therapy in this case, no ventricular fibrillation causing immediate cardiac further diagnostics have been recommended at this arrest.5,10 In people, sustained ventricular tachy- time. Because no underlying structural causes for cardias rarely occur in patients without underly- such a malignant ventricular arrhythmia were ing structural disease, but if structural disease is found, discontinuation of the sotalol with close absent, the prognosis is usually very good.5,10 monitoring will be considered in the future in The tiger in this case had paroxysmal ventricular event that the arrhythmia in this case was transient. flutter while anesthetized. Ventricular arrhythmias have been reported in a tiger immobilized with Acknowledgments: The authors would like to medetomidine and ketamine, and so the arrhyth- thank Dr. Edward Ramsey, Dr. James Steeil, Janet mia could possibly have been precipitated by Pezzi, the Anesthesia and Radiology services at anesthesia.4 In both cases, similar doses of keta- the University of Tennessee Veterinary Teaching mine were used (2.30 mg/kg in this case, compared Hospital, and the staff of Tiger Haven for their with 2.35 mg/kg in the previously reported case); assistance with this case. however, dexmedetomidine (11.5 lg/kg) was used in this case compared with medetomidine (30 lg/ LITERATURE CITED kg) in the previously reported case. The authors of the prior case reported that when a lower dose of 1. Britton, J. W., and E. Benarroch. 2006. Seizures medetomidine (18 lg/kg) was used for subsequent and syncope: anatomic basis and diagnostic consider- immobilizations on the same tiger, no ventricular ations. Clin. Auton. Res. 16: 18–28. arrhythmias were noted. 2. Chalkins, H., and D. P. Zipes. 2008. Hypotension and syncope. In: Libby, P., and E. Braunwald (eds.). Dexmedetomidine is the dextro-enantiomer of Braunwald’s Heart Disease: A Textbook of Cardiovas- the racemate medetomidine and is about twice as cular Medicine. Saunders/Elsevier, Philadelphia, potent as medetomidine, with similar sedation Pennsylvania. Pp. 975–984. 3 and analgesic effects. It is considered a safer 3. Donald, C. P., and D. C. Plumb. 2011. Plumb’s preparation than medetomidine because it does Veterinary Drug Handbook. PharmaVet, Stockholm, not contain the levo-enantiomer, levomedetomi- Wisconsin. dine, which appears to intensify the bradycardic 4. Forsyth, S. F., R. G. Machon, and V. P. Walsh. effects of medetomidine.11 Accounting for the 1999. Anaesthesia of a Sumatran tiger on eight greater potency of dexmedetomidine, the tiger in occasions with ketamine, medetomidine and isoflurane. this case would have received an equivalent of 23 NZ. Vet. J. 47: 105–108. lg/kg medetomidine, which is midway between 5. Goldberger, A. L. 2006. Clinical electrocardiog- the high and low doses of medetomidine given to raphy: a simplified approach. Mosby Elsevier, Phila- the previously reported tiger. delphia, Pennsylvania. Although the ventricular flutter may have been 6. Green, H. W., 3rd. 2008. Diagnosis and treatment of syncope. In: Proc. N. Am. Vet. Conf., Orlando, coincidental (i.e., anesthesia induced) rather than Florida. Pp. 221–223. being the true cause of collapse, this seems highly 7. Lyle, C. H., G. Turley, K. J. Blissitt, R. S. Pirie, I. unlikely given the recent history of episodic G. Mayhew, B. C. McGorum, and J. A. Keen. 2010. collapse occurring in the weeks prior to workup Retrospective evaluation of episodic collapse in the and the complete resolution of clinical signs after horse in a referred population: 25 cases (1995–2009). J. sotalol administration. Additionally, the tiger did Vet. Intern. Med. 24: 1498–1502. not experience recurrence of any arrhythmias 8. MacKie, B. A., R. L. Stepien, and H. B. Kellihan. during sedation for the follow-up ECG. For these 2010. Retrospective analysis of an implantable loop 504 JOURNAL OF ZOO AND WILDLIFE MEDICINE recorder for evaluation of syncope, collapse, or inter- agents. In: Riviere, J. E., and M. G. Papich (eds.). mittent weakness in 23 dogs (2004–2008). J. Vet. Veterinary Pharmacology and Therapeutics, 9th ed. Cardiol. 12: 25–33. Wiley-Blackwell, Ames, Iowa. Pp. 337–380. 9. McKeon, A., C. Vaughan, and N. Delanty. 2006. 12. Schnipper, J. L., and W. N. Kapoor. 2001. Seizure versus syncope. Lancet Neurol. 5: 171–180. Diagnostic evaluation and management of patients 10. Olgin, J., and D. P. Zipes. 2012. Specific arrhyth- with syncope. Med. Clin. N. Am. 85: 423–456. mias: diagnosis and treatment. In: E. Braunwald, E., 13. Tomas, B. G., and T. B. Garcia. 2004. Arrhyth- and R. O. Bonow (eds.). Braunwald’s Heart Disease: A mia Recognition: The Art of Interpretation. Jones and Textbook of Cardiovascular Medicine, 9th ed. Sa- unders, Philadelphia, Pennsylvania. Pp. 771–824. Bartlett Publishers, Sudbury, Massachusetts. 11. Posner, L. P., and P. Burns. 2009. Sedative agents: tranquilizers, alpha-2 agonists, and related Received for publication 30 August 2012