Wednesday, February 3, 2016

Managing Rate Control in the Face of Borderline Hypotension

Encountering patients in afib with RVR is a daily occurrence in the emergency department. Rate control with AV blocking drugs are standard approaches for stable patients and good ol’ electricity for those who are unstable. But there is a group in-between that presents a different challenge. Those who are in afib but are relatively hypotensive, by which I mean SBPs in the 90’s or low 100’s. In these patients, pharmacologic rate control may improve SBPs by slowing the ventricular rate sufficiently to allow for adequate filling and thus improve cardiac output. But that is almost always balanced by the risk of hypotension caused by drugs like diltiazem or metoprolol.

In order to avoid the initiation of amiodarone or digoxin, two drugs notorious for a myriad of short term adverse events, long term toxicity and clinically significant drug-drug interactions, there are certain strategies that seem to be overlooked. Those strategies include using low-dose diltiazem, extended bolus diltiazem, or esmolol. (Administration of calcium prior to CCB has been covered elsewhere, but is generally not regarded as effective.)
 
Traditional teachings of rate control with diltiazem quote doses starting at 0.25 mg/kg followed by 0.35 mg/kg if the first bolus is unsuccessful. While certainly effective and are associated with lower incidences of hypotension versus verapamil, these doses may be less than ideal in every patient. Individualizing doses for patients in this relative hypotension range poses a potential advantage. In one study from 2011, investigators randomized an ED population of patients presenting with afib + rvr to low (< 0.2 mg/kg), standard (> 0.2 to < 0.3 mg/kg) or high dose diltiazem (> 0.3 mg/kg) to achieve a positive clinical response defined as a reduction in ventricular response rate (VRR) to 100 bpm or a VRR reduction of at least 20% from baseline within 30 minutes.1 Safety was also assessed when episodes of SBP < 90, or reduction of at least 20% from baseline, respiratory failure requiring intubation, cardiac arrest or onset of unstable rhythms occurred within 30 minutes.

Patients who received low dose (0.14 mg/kg + 0.04) achieved a similar rate of overall clinical success (p = 0.605) but a lower incidence of overall complications (p = 0.025). This rate of overall complications was driven by a lower incidence of reductions of SBP by at least 20% between groups (low: 18.0%; standard: 33.7%; high 38.9%, p = 0.047). However, these patients were normotensive at the time of study drug administration, limiting the ability to extrapolate to the relative hypotensive population in question. Never the less, there is virtually no evidence, aside from scant case reports to go on. The authors concluded that this is a promising dosing alternative, but certainly not ready for widespread implementation.

A slightly different approach to diltiazem in this scenario is a bolus-from-the-bag approach. Credit to emcrit (http://emcrit.org/podcasts/crashing-a-fib/) for pointing in this direction in an old podcast, administering diltiazem 2.5mg/min (maximum 50 mg, or 20 minutes) until desired HR is achieved. Although studied in an SVT, this seems to be a reasonable approach that maximizes dose but can limit hypotension by infusing the bolus much slower than would normally be done in the ED.2


Esmolol is on its way to being one of the ED’s new favorite drugs (at least in my opinion). As a result of its relative "newness" and the association of it with the high cost during its branded days, esmolol is often not thought of as a therapeutic option. But over recent years, esmolol has developed a following for its novel application in septic shock and refractory ventricular fibrillation.3,4 Although, afib with RVR still underutilizes this drug particularly in the relative hypotensive patient. Taking advantage of it’s rapid-on, rapid-off kinetics (onset in seconds with a half-life of ~ 9 minutes), if hypotension were to occur it could quickly be shut off. Evidence is lacking, unfortunately, in the ED, let alone in the relative hypotensive patient. Most research with this drug comes from PACU/post-op settings with limited generalizability. However, the pharmacology/kinetics and lack of alternatives make it a promising option.

Critical to the effectiveness of esmolol is administering the bolus. I’ve experienced (anecdotally) if 500 mcg/kg is recommended, it’s perceived to be a high dose and avoided. But simply taking advantage of the metric system, and recommending 0.5 mg/kg followed by the drip at 50 mcg/kg/min tends to be more successful.

There is no good answer in choosing a rate control strategy for the afib with rvr patient who’s SBP is in the 90’s to low 100’s and otherwise not hemodynamically unstable. Most of the time, slowing the ventricular rate will improve the patients SBP, but there may an opportunity to use alternative dosing strategies for diltiazem or another drug altogether in esmolol.

References:
  1. Lee J, et al. Low-dose diltiazem in atrial fibrillation with rapid ventricular response. Am J Emerg Med. 2011 Oct;29(8):849-54.
  2. Lim SH, et al. Slow-infusion of calcium channel blockers in the emergency management of supraventricular tachycardia. Resuscitation. 2002 Feb;52(2):167-74.
  3. Morelli A, et al. Effect of heart rate control with esmolol on hemodynamic and clinical outcomes in patients with septic shock: a randomized clinical trial. JAMA. 2013 Oct 23;310(16):1683-91.
  4. Driver BE, et al. Use of esmolol after failure of standard cardiopulmonary resuscitation to treat patients with refractory ventricular fibrillation. Resuscitation. 2014 Oct;85(10):1337-41.

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