Please note: The following ECG has been recorded at 25 mm/sec and gain setting of 10 mm/mV.
A 73-year-old female collapsed in the Outpatient Radiology Department where she had been waiting to have a CT coronary angiogram. She had been given 160 mg verapamil to slow her heart rate for the scan.
Her usual medications included sotalol 80 mg twice a day.
On arrival of the Rapid Response Team she was drowsy, cold and peripherally shut down with systolic blood pressure 60 mmHg. Her arterial blood gas results at the scene are below, and her ECG is shown on page 3 (Figure 1).
Parameter |
Patient Value |
Adult Normal Range |
Fi02 |
0.5 |
|
pH |
7.05* |
7.35 — 7 45 |
pCO2 |
40.4 mmHg (5.3 kPa) |
35.0 - 45.0 (4.6 - 6.0) |
pO2 |
221 mmHg (29.1 kPa) |
|
SpO2 |
98% |
|
Bicarbonate |
10.5 mmol/L• |
22.0-26.0 |
Base Excess |
-17.9 mmol/l-• |
-2.0- +2 0 |
Lactate |
8.0 mmol/L* |
0.5- 1 6 |
Sodium |
132 rnmol/l_• |
135 - 145 |
Potassium |
5.4 mmol/L* |
3.5 - 5.0 |
Chloride |
105 mmol/L |
95 - 105 |
Glucose |
5.3 mmol/l- |
3.5 - 6.0 |
Give the likely underlying cause for the patient's collapse. (10% marks)
Interpret the investigations. (20% marks)
Outline specific therapies for the management of this patient, indicating the doses and mechanisms of action for any pharmacotherapy you have listed. (70% marks)
a) Cardio-toxicity from a combination of a beta-blocker and calcium channel blocker resulting in
cardiogenic shock.
Candidates may include a differential diagnosis – MI and cardiogenic shock not unreasonable.
b) Metabolic (lactic) acidosis with inadequate respiratory compensation
A-aDO2 approx 85 mmHg – raised for 73-year-old
Junctional bradycardia (but much slower than expected). Ventricular escape rhythm
acceptable. Peri arrest.
c) Specific therapies
Statement on resuscitation (Rapid ABC; iv access; O2, start CPR if indicated, monitor, rapid
echo).
Multiple agents often required with stepwise approach.
• Atropine 1mg stat (can be repeated x 3; often ineffective; muscarinic receptor
antagonist increases SA node discharge, conduction through the AV node and opposes
action of Vagus nerve)
• Adrenaline or Noradrenaline infusion starting at 10-20 g/min and titrate to a MAP > 65
mmHg (+ve inotropy, chronotropy, vasoconstriction)
• Calcium – Chloride or Gluconate can be given (more calcium in CaCl) – 10mls of 10%
solution (can be repeated x3 +/- infusion; competitively increases calcium entry into the
myocardium via non-blocked channels)
• Glucagon 5mg stat (can be repeated x3; increases intracellular cAMP and has been
shown to increase heart rate in BOTH beta-blocker and CCB toxicity).
• 100mls 8.4% NaHCO3 stat (she is already very acidotic)
• Hyperinsulinaemia-Euglycaemia – short acting insulin 1 unit/kg with 50mls 50%
Dextrose bolus, then 0.5 units insulin /kg/hr with 10% dextrose infusion and q1hrly BGLs
and K+ (high dose insulin = +ve inotrope but mechanism not clearly understood)
• Lipid Emulsion – 1ml/kg 20% lipid emulsion bolus (can be repeated x 3 then start
infusion 0.5mls/kg/min; acts as a “lipid sink” surrounding lipophillic drugs rendering them
ineffective & maybe fatty energy source for myocardium)
Other Therapies
• Trans-cutaneous pacing
• Trans-venous temporary pacing.
• VA-ECMO
Additional Examiners’ Comments:
Many candidates failed to interpret the ECG, or to discuss the mechanism of therapies. Basic
knowledge gaps in many answers.
The image used in this SAQ is not from the original college paper (those are a sacred and jealously guarded resource). Fortunately, the ECG I found at LITFL is virtually identical.
In short, the underlying cause of the collapse is simultaneous calcium channel blocker and beta blocker overdose, a variant on the theme of toxic antiarrhythmic polypharmacy.
To interpret the investigations:
As to management: the college asked to outline specific therapies, i.e. not supportive ones. For the management of combined beta blocker and calcium channel blocker toxicity, this would really consist of the following strategies:
Management | Dose and rationale |
Decontamination with activated charcoal |
1g/kg of charcoal; because it may slow the absorption of some beta-blockers and calcium channel blockers. |
Calcium infusion |
0.2mmol/hr. |
High-dose insulin |
0.5-2.0 unit/kg/hr, as well as whatever amount of dextrose is required to maintain normoglycaemia. This is becoming the standard of care (Woodward et al, 2014) Why?
|
Glucagon |
May be effective (eg. Doyon et al, 1993) but is not recommended as a first-line agent. |
Intralipid |
Lipid emulsion should "decontaminate" the bloodstream by making these highly lipophilic drugs less bioavailable (true for most of them, with the exception of atenolol and sotalol). Verapamil toxicity is listed as one of the indications for the use of lipid emulsion in toxicology(Cave and Harvey, 2009). |
In addition, generic supportive therapies can be listed, although they may not attract any marks:
Nawrath, H., et al. "Class I Antiarrhythmic Drug Effects: What Is the Basis for Subgroups Ia, Ib and Ic." Cardiac Arrhythmias: The Management of Atrial Fibrillation (2013): 39.
Vaughan-Williams, E. M. "Classification of antiarrhythmic drugs." Cardiac arrhythmias 449 (1970).
Rosen, Michael R. "The sicilian gambit-a new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms." Circulation 84.4 (1991): 1831-1851.
Kowey, Peter R. "Pharmacological effects of antiarrhythmic drugs: Review and update." Archives of internal medicine 158.4 (1998): 325-332.
Siddoway, L. A., P. J. Podrid, and P. R. Kowey. "Pharmacologic principles of antiarrythmic drugs." (1995): 355-368.
Yamreudeewong, Weeranuj, et al. "Potentially significant drug interactions of class III antiarrhythmic drugs." Drug safety 26.6 (2003): 421-438.
Strauss, William E., and Alfred F. Parisi. "Combined Use of Calcium-Channel and Beta-Adrenergic Blockers for the Treatment of Chronic Stable AnginaRationale, Efficacy, and Adverse Effects." Annals of internal medicine 109.7 (1988): 570-581.
Markota, Andrej, et al. "Treatment of near-fatal beta blocker and calcium channel blocker intoxication with hyperinsulinemic euglycemia, intravenous lipid emulsions and high doses of norepinephrine." Signa Vitae 10.1 (2015): 144-150.
Woodward, Christina, Ali Pourmand, and Maryann Mazer-Amirshahi. "High dose insulin therapy, an evidence based approach to beta blocker/calcium channel blocker toxicity." Daru 22.36 (2014): 2008-223.
Henry, Philip D. "Comparative pharmacology of calcium antagonists: nifedipine, verapamil and diltiazem." The American journal of cardiology 46.6 (1980): 1047-1058.
Doyon, Suzanne, and James R. Roberts. "The use of glucagon in a case of calcium channel blocker overdose." Annals of emergency medicine 22.7 (1993): 1229-1233.