Author: Brent N. Reed, PharmD, BCPS-AQ Cardiology, FAHA

“[Intravenous diltiazem] is a terrible drug. It ought to be removed from the formulary.”
From the head of electrophysiology at my previous institution

To begin, I should clarify that my opposition to diltiazem infusions (i.e., “dilt drips”) is related to their use for acute rate control in patients with underlying cardiovascular disease. There are some settings (e.g., general medicine, emergency medicine), where the temporizing use of a diltiazem infusion may be appropriate, assuming the drug can be properly managed. However, in patients with a history of coronary artery disease, heart failure with reduced ejection fraction (HFrEF), or a variety of other chronic cardiovascular conditions, diltiazem infusions are rarely ideal.

First, several pharmacokinetic characteristics make diltiazem a suboptimal agent to administer as a continuous intravenous infusion. Its delayed onset of action requires the administration of bolus doses at initiation and with each rate increase. Unfortunately, these are often omitted, which can mislead clinicians into believing that the initial rate is inadequate. As a consequence, doses are often rapidly escalated, long before the full effects of the previous rate have been realized. Additionally, diltiazem does not demonstrate linear pharmacokinetics, so changes in dose rarely correlate with its effects on heart rate or blood pressure. The drug’s long half life also increases the risk of accumulation with prolonged use. Minimal evidence supports the use of diltiazem infusions beyond 24 hours, thus little guidance exists for their practical management when used for extended periods of time.1

Second, as a continuous infusion, there is a tendency to believe that diltiazem can be rapidly titrated; this, combined with the aforementioned pharmacokinetic characteristics, make it a commonly mismanaged agent in the acute care setting. Given its delayed onset of action, a weight-based bolus should be administered prior to the initiation of a continuous infusion. Although the package insert recommends a 0.25 mg/kg bolus, this often results in hypotension, and may explain why bolus doses are often omitted. I usually recommend starting with a 0.15 mg/kg bolus and then administering additional boluses if necessary, although some evidence suggests that pre-medicating with intravenous calcium may mitigate the risk of hypotension. As I alluded to above, when bolus doses are omitted, the tendency is to rapidly increase the rate of infusion. Although a therapeutic effect may be observed at 1-2 hours, significant accumulation occurs as the drug approaches steady state 4-6 hours later, increasing the risk for adverse effects (e.g., precipitous changes in heart rate or blood pressure, high-degree atrioventricular block) that may persist for 10-12 hours or more. Furthermore, this delay to steady state is also why diltiazem infusions should not be titrated to effect.

Third, in many patients with significant underlying cardiovascular disease, diltiazem is rarely an ideal long-term strategy for rate control. Although the negative inotropic effects of diltiazem are probably no worse than beta blockers in the acute setting, it does not confer the same long-term benefits associated with beta blockers across several cardiovascular conditions, such as reductions in the risk of sudden cardiac death among those with prior myocardial infarction,2 or improvements in all-cause mortality in patients with HFrEF.3 In fact, in this latter population, the use of diltiazem is actually associated with a nearly twofold increase in the risk of worsening heart failure.4

Proponents of diltiazem infusions will often argue that its disadvantages are related to chronic administration and this should not preclude its use in an acute setting.  While I agree its acute risks are probably no worse than beta blockers, why even start down a path that does not represent a long-term solution (when reasonable alternatives exist), especially given the practical limitations associated with its use? Moreover, if diltiazem is successful in the immediate setting, will therapy be continued? If not, how quickly can a more definitive management strategy be implemented? Should a patient’s length of stay be extended solely for the purposes of cross-titrating to a more appropriate long-term strategy? My point is this: if no plans for a more definitive strategy exist, and there are no plans to continue diltiazem in the long-term, it is actually a step backward to start with it.

There are some scenarios where diltiazem infusions are a reasonable approach, such as a short-term infusion to maintain hemodynamic stability as a patient awaits more definitive management (e.g., ablation), or as a transition to oral therapy in a patient without structural heart disease, in whom diltiazem is a reasonable agent for long-term rate control.  However, even in these scenarios, caution should still be exerted in terms of its practical management in order to reduce the risks associated with drug accumulation.

Note: This post is an updated version of an entry originally written in August 2013 for my personal blog. Although I have made some changes to the writing style, no changes to the content have been made.

 

 
Brent N. Reed, PharmD, BCPS-AQ Cardiology, FAHA

Dr. Reed is an assistant professor in the Department of Pharmacy Practice and Science at the University of Maryland School of Pharmacy, and practices as a clinical pharmacy specialist in advanced heart failure at the University of Maryland Medical Center in Baltimore, MD. Follow him on Twitter @brentnreed

 

References

  1. Diltiazem HCl Powder for Solution [package label]. Lake Forest, IL: Hospira, Inc; 2008.
  2. Turi ZG,Braunwald E.The use of beta-blockers after myocardial infarction. JAMA.1983 May 13;249(18):2512-6.
  3. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999 Jun 12;353(9169):2001-7.
  4. Goldstein RE, et al; for the Adverse Experience Committee and the Multicenter Diltiazem Postinfarction Research Group. Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. Circulation. 1991 Jan;83(1):52-60.
The Trouble with Diltiazem Infusions
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