1. Diltiazem overdose in a 14-year-old Labrador Lisa Fiorenza Clinical Advisor: Dr. Bruce Kornreich Pre-clinical Advisor: Dr. Wayne Schwark Special thanks: Dr. Josh Smith, Dr. Freddie Brewer

2. Signalment/Chief Complaint 14 year old Spayed female Yellow Labrador Collapse episodes Arrhythmia at rDVM

3. History 3 episodes of collapse over 2.5 wks –Vocalizes prior –Relatively normal before and after episodes Lethargic since

4. History At rDVM –Arrhythmia ausculted –Chem: BUN= 37 [10-32], ALT= 253 [20-98], Alk Phos= 454 [17-111] –Baseline T4= 0.9 ug/dL [1.5-3] –Chest rads: suspect cardiomegaly –ECG: ventricular tachycardia –Sotalol 1.5 mg/kg PO q12 hrs initiated

5. Initial Exam QAR, transported into ER on gurney Irregularly irregular rhythm –HR varied from 60 bpm to 240 bpm Poor pulses w/ deficits Abdominal fluid wave

6. Diagnostics Gaslyte, QATS, blood smear –Mild respiratory alkalosis 4DX –Anaplasma positive Mild peritoneal fluid on FAST scan –Modified transudate MAP 110 mmHg on Cardell Troponin –0.77 ng/dL [0-0.1]

7. Dr. Brewer’s last emergency call! ECG –HR 115-250 bpm –Sinus rhythm w/ frequent paroxysms of SVT –Short P-R interval, wide QRS complexes, +/- delta waves –Right axis shift

8. Our patient’s ECG

9. Dr. Brewer’s last emergency call! Echo –Dilated LV, normal LA –Mild systolic dysfunction Near-normal when in sinus rhythm –Dilated pulmonary veins –Mild MVD with mild regurgitation –Normal right heart, pericardium, outflow velocities

10. Decreased systolic function

11. Problems 1.Collapse x3 2.Tachyarrhythmia – Supraventricular vs ventricular 3.Poor pulses w/ deficits 4.Mild myocarditis –Tachycardiomyopathy suspected 5.Mildly decreased systolic function Lethargy Hypothyroid Mild liver enzyme elevations Anaplasma positive

12. Diagnosis Wide complex tachycardia with suspected secondary tachycardiomyopathy Rule outs: –Wolff-Parkinson White syndrome (SVT) –Ventricular tachycardia (VT)

13. Treatment Sotalol 1.5 mg/kg –Class III: Potassium channel blocker Prolongs repolarization time –Also a non-selective Beta-blocker Decreases HR Diltiazem ~2 mg/kg –Class IV: Calcium channel blocker (CCB) Decreases SA node discharge Decreases AV node conduction For suspected Wolff-Parkinson White syndrome

14. Diltiazem Four 60 mg pellets per capsule

15. Diltiazem overdose Received 4x dose (~9 mg/kg) of Diltiazem extended release capsule

16. Diltiazem overdose Four hours later, patient obtunded in ICU kennel HR= 30 bpm Techs unable to get blood pressure Cardiology & E/CC called –Flash echo Bradycardia, decreased contractility –ECG…

17. Diltiazem Overdose HR ~ 45 bpm Gave atropine dose

18. Uh oh… HR ~ 15 bpm

19. And then…

20. Compressions & RoSC HR ~ 110 bpm

21. We fixed her!… Sort of

22. Calcium channel action SA and AV node! Ca channel opens Ca influx stimulates SR release of lots more Ca Muscle contraction occurs Courtesy of ABPI

23. Calcium Channel Blocker Uses Benzothiazepines (diltiazem) –Supraventricular tachycardias –Acute renal failure Dihydropyridines (amlodipine) –Hypertension Vascular-selective

24. Diltiazem MOA Blocks influx of Ca through L-type (long-lasting) Ca channels of pacemaker cells especially –Slows SA node activity –Decreases AV node conduction –Minimal vasodilation (intermediate selectivity) Ultimately, decreases HR and prolongs refractory period –Good if you’re tachycardic, bad in excess…

25. CCB overdose signs Bradycardia & decreased contractility Decr Cardiac output Hypotension Shock Death

26. CCB Overdose treatment theories http://www.ajhp.org/content/63/19/1828/F1.expansion  

27. CCB Overdose treatments Decontamination (asymptomatic) –Emesis –Charcoal + cathartic 2-4 times in 24 hrs for extended-release capsules Supportive –IVF, colloids

28. CCB Overdose treatments What works –Pressor (sympathomimetics) CRIs Epi, dobutamine, dopamine, norepi, isoproterenol –High-dose insulin CRI (+ dextrose) –Lipid emulsion What doesn't –Atropine –Glucagon –Ca gluconate?

29. DoBUTamine MOA Sympathomimetic –Direct stimulation of  1 receptors Positive inotrope (  cardiac contractility) Positive chronotrope (  HR) Titrate up to effect, then wean off while monitoring

30. Back to our patient Epinephrine during code brought her back Marked bradycardia & hypotension –Dobutamine CRI: started at 5 mcg/kg/min, titrated up to effect (15 mcg/kg/min) –Successfully weaned off after ~ 20 hrs –Monitored HR, BP, continuous ECG, electrolytes

31. 3 days later… There’s our girl!

32. Cost ER Visit: $350 ER Cardio exam & echo: $490 Diagnostics/treatment*:$700 Holter monitor:$250 Costs assoc w/ overdose:$1600 TOTAL:$3,390 - $1,600= $1,790 *1st night in ICU + anything not affected by overdose

33. Moral of the story? ALWAYS read the Rx labels AND tx sheet Nobody’s perfect! –Honesty saved her life

34. References Malouin, A. and King, L. (2009). Ca Channel and Beta Blocker Drug Overdose. In D. Silverstein and K. Hopper, Small Animal Critical Care Medicine (357-62). St. Louis, MO: Saunders. Hayes, C. and Knight, M. (2012). Calcium Channel Blocker Toxicity in Dogs and Cats. Vet Clin Small Anim, 42(2), 263-277. Cooke, K.L. and Snyder, P.S. (1998). Calcium Channel Blockers in Veterinary Medicine. J Vet Intern Med 12, 123-131. American College of Emergency Physicians. (1995). Clinical policy for the initial approach to patients presenting with acute toxic ingestion or dermal or inhalation exposure. Ann Emerg Med. 25, 570-85. Kornreich, B. (2012, November). Mechanisms of Arrhythmia. Block 5. Lecture conducted from Ithaca, NY.

35. Questions? Thank you!! Bruce Kornreich Wayne Schwark Josh Smith Freddie Brewer Thank you!! Family Friends c/o 2014