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

Signalment/Chief Complaint

• 14 year old • Spayed female• Yellow Labrador• Collapse episodes• Arrhythmia at rDVM

History

• 3 episodes of collapse over 2.5 wks– Vocalizes prior– Relatively normal before and after episodes

• Lethargic since

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

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

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]

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

Our patient’s ECG

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

Decreased systolic function

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Problems

1. Collapse x32. Tachyarrhythmia

– Supraventricular vs ventricular

3. Poor pulses w/ deficits4. Mild myocarditis

– Tachycardiomyopathy suspected

5. Mildly decreased systolic function

• Lethargy• Hypothyroid• Mild liver enzyme elevations• Anaplasma positive

Diagnosis

• Wide complex tachycardia with suspected secondary tachycardiomyopathy

• Rule outs: – Wolff-Parkinson White syndrome (SVT)– Ventricular tachycardia (VT)

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

Diltiazem

• Four 60 mg pellets per capsule

Diltiazem overdose

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

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…

Diltiazem Overdose

HR ~ 45 bpm

Gave atropine dose

Uh oh…

HR ~ 15 bpm

And then…

Compressions & RoSC

HR ~ 110 bpm

We fixed her!… Sort of

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

Calcium Channel Blocker Uses

• Benzothiazepines (diltiazem)– Supraventricular tachycardias– Acute renal failure

• Dihydropyridines (amlodipine)– Hypertension

• Vascular-selective

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…

CCB overdose signs

Bradycardia & decreased contractility

Decr Cardiac output

Hypotension

Shock

Death

CCB Overdose treatment theories

http://www.ajhp.org/content/63/19/1828/F1.expansion

CCB Overdose treatments

• Decontamination (asymptomatic)– Emesis– Charcoal + cathartic

• 2-4 times in 24 hrs for extended-release capsules

• Supportive– IVF, colloids

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?

DoBUTamine MOA

• Sympathomimetic– Direct stimulation of 1 receptors

• Positive inotrope ( cardiac contractility)• Positive chronotrope ( HR)

• Titrate up to effect, then wean off while monitoring

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

3 days later…

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are needed to see this picture.

There’s our girl!

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

Moral of the story?

• ALWAYS read the Rx labels AND tx sheet

• Nobody’s perfect!– Honesty saved her life

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.

Questions?

Thank you!!Bruce Kornreich

Wayne Schwark

Josh Smith

Freddie Brewer

Thank you!!

Family

Friends

c/o 2014