"[Intravenous diltiazem] is a terrible drug. It ought to be removed from the formulary."
- Head of electrophysiology at my previous institution
As I begin, I think it is important to clarify that much of my opposition to diltiazem infusions (i.e., "dilt drips") is based on their use for acute rate control in patients with significant underlying cardiovascular disease. There are other settings (e.g., general medicine, emergency medicine), where the temporizing use of a diltiazem infusion may be an appropriate strategy, assuming the drug is properly managed from a practical standpoint. However, in patients with a history of coronary artery disease, heart failure with reduced ejection fraction (HFrEF), and other chronic cardiovascular conditions, diltiazem infusions are rarely an ideal strategy.
First, several pharmacokinetic characteristics make intravenous diltiazem a suboptimal agent to administer as a continuous infusion. Its delayed onset of action necessitates the administration of bolus doses with the initiation of a continuous infusion and with each rate increase. Unfortunately, these are often omitted, which may lead clinicians to believe an infusion is inadequate at its current rate (and often resulting in rapid dose escalation). Additionally, its long-half life increases the risk of accumulation with prolonged use, especially with rapid dose escalation. Finally, diltiazem does not demonstrate linear pharmacokinetics, so changes in dose rarely correlate with its therapeutic effects. Minimal (if any) evidence supports the use of diltiazem infusions beyond 24 hours, giving little guidance to clinicians on its practical management .
Second, as a continuous infusion, there is a tendency to believe that diltiazem can be titrated like a rapidly-acting vasoactive agent; 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 (i.e., 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 an 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 , or improvements in all-cause mortality in patients with HFrEF . 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 .
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 not plans to continue an agent in the long-term, it just seems like a step backward to even start there.
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.
- Diltiazem HCl Power for Solution [package label]. Lake Forest, IL: Hospira, Inc; 2008.
- Turi ZG,Braunwald E.The use of beta-blockers after myocardial infarction. JAMA.1983 May 13;249(18):2512-6.
- 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.
- 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.