Critically  evaluate  the  role  of anti-arrhythmic drugs in the  management of cardiac arrest.

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College Answer

Several antiarrhythmic drugs are recommended in the ARC guidelines for use in VF/pulseless VT cardiac arrests and for bradycardia/asystole. However no drugs have been shown to improve long- term survival after cardiac arrests. Basic and advanced life support, early access to defibrillation and treatment of reversible causes take priority.

Guideline recommended drugs that should be considered include:

Lignocaine 1-1.5mg/kg, Amiodarone 300mg, Magnesium 5 mmol and atropine (1-3 mg).

Lignocaine is a class 1 antiarrhythmic, sodium channel blocker and has been traditionally used in VF/ pulseless VT cardiac arrest and while it is listed as first line in the ARC guidelines, the evidence for its use is limited. It should be given as a bolus for refractive VF/VT and occasionally can be used when the patient has recurrent VF/VT to prevent recurrence. Prophylactic use in AMI not complicated by arrhythmia is not recommended as there is some evidence that it may worsen overall prognosis.

Amiodarone is a complex antiarrhythmic drug with effects on sodium, potassium and calcium channels and alpha and beta blocking effects. It is an effective antiarrhythmic agent for both supraventricular and ventricular arrhythmias and it also causes less cardiac depression than other antiarrhythmics. It thus has some advantage over lignocaine. It is toxic to the tissues if it extravasates and is recommended for central venous administration but administration into an antecubital vein in the cardiac arrest situation is acceptable. Bolus injection of 300mg can be

followed by 150 mg if no effect and can be followed by infusion. Amiodarone has been shown to be better than placebo and lignocaine in terms of survival to hospital admission after out of hospital cardiac arrest due to refractory VF.

Magnesium is recommended by the ARC particularly for: Torsades de points, digoxin toxicity, and demonstrated hypokalemia/hypomagnesemia. It can be given as a 5mmol bolus which can be repeated and followed by infusion. There are no clinical studies using magnesium in this setting but it has been demonstrated to be a useful antiarrhythmic in postoperative cardiac surgical patients (Level 1 evidence).

Atropine is recommended by the ARC for use in severe bradycardia and in asystole. There are no controlled or randomised studies supporting its use. It can be given in 1 mg boluses up to 3 mg.

Discussion

This question, written in 2005, pre-dates the changes in ARC guidelines which have done away with lignocaine and atropine, leaving behind only amiodarone. This drug now occupies a shaky position after the third cycle of CPR for a shockable rhythm; the objective of using it is really to convert a defibrillation-refractory VF into one which is defibrillation-sensitive.

The evidence for its use is supported by two trials (Dorian et al 2002, and Somberg et al 2002) which found some benefit of amiodarone over lignocaine in the context of shock refractory or recurrent VT and VF. There was no benefit in survival to hospital discharge, but there was some benefit in survival to hospital admission. This better than the evidence for any other anitarrhytmic drug, and thus amiodarone remains in the guidelines ...for now.

All of this information is available in the ARC Guideline 11.5: Medications in Adult Cardiac Arrest. In brief summary, other drugs which are covered by this guidelines statement are as follows:

  • Adrenaline: Favoured because retrospective studies have found an improvement in the rates of ROSC with adrenaline; however there has never been any confirmed improvement in survival associated with it.
  • Calcium: Not recommended routinely; no benefit in terms of survival (6.8mmol calcium chloride as a bolus)
  • Lignocaine: Not as good as amiodarone, and thus recommended only for those situations when amiodarone cannot be used (1mg/kg bolus)
  • Magnesium: Recommended for torsades des pointes, but not recommended for any other situation, as there is no survival benefit. (5mmol bolus)
  • Potassium: Recommended for hypokalemic arrests only (5mmol bolus)
  • Sodium bicarbonate: Not recommended, as it is associated with poor short-term and long-term outcomes.
  • Vasopressin: Not recommended as an alternative to adrenaline, as there is insufficient data to support its use.
  • Aminophylline: There is no evidence of harm, but there is insufficient evidence to recommend its routine use.
  • Thrombolytics: Recommended only in confirmed or strongly suspected massive PE as a cause of cardiac arrest, in which case one is committed to performing CPR for 60-90 minutes.

Rationale for the use of antiarrhythmic drugs in cardiac arrest

  • Cardiac arrest is often the consequence of a non-perfusing arrhythmia. Ergo, an antiarrhythmic drug is the correct treatment.
  • The energy required to defibrillate is decreased by acute administration of amiodarone (in dogs - Fain et al, 1987)
  • The use of anti-arrhythmics may not be guided by any scientific principles, but it appears so deeply ingrained that it has become accepted as standard practice. Therefore to abjure the use of antiarrhythmics would be viewed as a substantial departure from standard practice. What would the coroner say?

Arguments against the use of antiarrhythmic drugs in cardiac arrest

  • Pro-arrhythmic properties of antiarrhythmics must be taken into account; even amiodarone can produce QTc prolongation and torsade.
  • The addition of extra drugs or steps to the algorithm complicates it, and makes it more difficult to teach (and to follow).
  • The improvement of survival to hospital admission may not translate into any improvement in survival (in fact, none of the studies have found any improvement in survival)
  • All the trials involving athiarrhythmics have compared one drug to another; there have been no placebo-controlled trials. We do not know what would happen without these drugs. Would survival rates drop sharply?

References

References

ARC Guideline 11.5: Medications in Adult Cardiac Arrest

 

Levine, Joseph H., et al. "Intravenous amiodarone for recurrent sustained hypotensive ventricular tachyarrhythmias." Journal of the American College of Cardiology 27.1 (1996): 67-75.

 

Dorian, Paul, et al. "Amiodarone as compared with lidocaine for shock-resistant ventricular fibrillation." New England Journal of Medicine 346.12 (2002): 884-890.

 

Skrifvars, M. B., et al. "The use of undiluted amiodarone in the management of out‐of‐hospital cardiac arrest." Acta anaesthesiologica scandinavica 48.5 (2004): 582-587.

 

Somberg, John C., et al. "Intravenous lidocaine versus intravenous amiodarone (in a new aqueous formulation) for incessant ventricular tachycardia." The American journal of cardiology 90.8 (2002): 853-859.

Kudenchuk, Peter J., et al. "Amiodarone for resuscitation after out-of-hospital cardiac arrest due to ventricular fibrillation." New England Journal of Medicine 341.12 (1999): 871-878.

Ong, Marcus Eng Hock, Tommaso Pellis, and Mark S. Link. "The use of antiarrhythmic drugs for adult cardiac arrest: a systematic review." Resuscitation 82.6 (2011): 665-670.

Huang, Yu, et al. "Antiarrhythmia drugs for cardiac arrest: a systemic review and meta-analysis." Crit Care 17.4 (2013): R173.

Fain, Eric S., John T. Lee, and Roger A. Winkle. "Effects of acute intravenous and chronic oral amiodarone on defibrillation energy requirements." American heart journal 114.1 (1987): 8-17.