Question 2

Created on Mon, 06/05/2017 - 21:48
Last updated on Mon, 07/24/2017 - 02:06
Pass rate: 40%
Highest mark: 6.9

Other SAQs in this paper

Other SAQs on this topic

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

CHB from LITFL

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)

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College answer

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.

Discussion

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:

  • Sightly raised A-a gradient (85 mmHg)
  • Acidaemia
  • The CO2 is contributing to the acidaemia
  • There is metabolic acidosis (SBE is -17.9)
  • No respiratory compensation (the expected CO2 is about 23.75 by Winter's rule, or around 22 if you use SBE to calculate it)
  • The anion gap is (132 + 5.4 - 105 - 10.5) = 21.9, elevated even if we don't know the albumin
  • The delta ratio (assuming albumin is 40) = 0.73, i.e. there is a mixed high and normal anion gap metabolic acidosis - some of this can be attributed to the raised lactate.
  • The ECG demonstrates a complete heart block. The college ECG was not much different (they called their a "junctional bradycardia" as there were no P waves).
  • Vital signs and examination findings suggest cardiogenic shock with very poor cardiac output (drowsy, cool extremities, hypotensive etc).
  • The glucose is normal, which is weird - but the competing effects may have balanced each other out (beta-blockers cause hypoglycaemia and CCBs cause hyperglycaemia).

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.
Calcium is a direct antagonist to calcium channel blockers.
Need to monitor phosphate levels, as they will drop.

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?

  • CCBs cause a decreased uptake of glucose into the myocardium
  • Activating insulin receptors bypasses the G-protein-coupled beta-receptors and activates the second messenger system (cAMP), promoting contractility 
  • Calcium channel blockers cause hypoinsulinaemia because insulin release is regulated by calcium entry into islet beta cells via L-type channels
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:

  • Intubation for the patient with propanolol-induced coma or seizures
  • Mechanical ventilation to help manage the pulmonary oedema which can develop. It also reduces the whole-body oxygen demands (in presence of severely depressed cardiac function).
  • Vasopressors and inotropes  may be useful in some cases, but there will always the the possibility of disaster. For example, the administration of adrenaline for a β-1 selective blocker overdose. A large dose of adrenaline will be required to achieve a given chronotropic effect because of the presence of a competitive antagonist. This large dose of adrenaline will then go on to have a massive and unopposed α-1 agonist effect, and the patient's head will explode.
  • Milrinone particularly has been used in the past, and can be viewed as a legitimate option which ought to be tried before you go with IABP or ECMO
  • Transvenous pacing may be possible, but the ventricle may not capture; and when it captures it may not respond with vigorous contractions, but rather with a limp sort of twitching. 
  • IABP has been used in cases where nothing you do seems to help, and particularly in case where there has been a calcium channel blocker co-ingestion
  • ECMO may be the only answer to a complete failure of the circulation.
  • Magnesium supplementation to prevent torsade de pointes
  • Phosphate supplementation to enhance inotropy and counteract the effects of the calcium infusion
  • Sodium bicarbonate to reverse the QRS prolongation (and, as the college pointed out, "she is alerady very acidotic"

References

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.