Month: October 2014

I think that given the very name of this blog and what it represents, it would be extremely remiss if I did not write about such a historic event that unfolded at the annual meeting of the American College of Emergency Physicians (ACEP), which is currently being held in Chicago this week.

For the first time, ACEP is now recognizing and supporting the presence and various roles EM pharmacists as members of the multidisciplinary team in the emergency department. This was passed in the form of a resolution (number 44, for those of you who are curious) at the council meeting held earlier this week at the conference.

Seeing some of the reactions that unfolded when the news broke on Twitter two days ago, this was a “Duh!” moment for many folks. For a service that has been around for 40-some years, this is quite a feat and has actually made some folks wonder why ACEP never officially recognized us EM pharmacists up until this moment. I think if you speak to any provider who has a dedicated EM pharmacist, he or she will sing praises related to the value of their EM pharmacist(s) within their department. But to have an official non-pharmacy body recognize us as valued clinicians in the emergency department – and our own EM physician colleagues at that – well, it is pretty amazing, to say the least.

A group of individuals served as part of a subcommittee for this initiative from the Section Advisory Group on Emergency Care of the American Society of Health-System Pharmacists (on Twitter at @ASHP_EMPharm), and they were instrumental in drafting, finalizing, and presenting the resolution, and we owe them a great deal of gratitude for all of their efforts in putting this together over the past year.

You may be wondering, “What are the implications of the passage of this resolution?” To say the least, there are many, but I think it is too early to tell how events will unfold. More than anything, this is a resolution for support of pharmacy services in the emergency department, but there are several possibilities. Over the past several years, we have witnessed a significant increase in the presence and expansion of pharmacy services across emergency departments in various regions of the United States, and we can only expect that this will continue. In addition, the number of emergency medicine pharmacy residencies, where pharmacists complete post-graduate hands-on training in the discipline of emergency medicine, has exploded over the past several years, with the current number of programs across EDs in the United States is nearly 30 (and counting). Growth in research collaborations and scholarly activities will also undoubtedly develop as a result of the passage of this resolution.

With this resolution successfully passed, the work has not ended; if anything, it has only just begun for us. Now more than ever, justification of our services in the emergency department will be paramount, which I envision will get down to the nuts and bolts of defining who we are and what we do. However, I think it is equally as important to ask ourselves how we can become even more innovative in the services that we provide and roles for which we wear many different hats beyond those that we do already on a day-to-day basis. Just as it has evolved for the past 40 years, our current practices as EM pharmacists may look very different over the same time frame of years down the road, perhaps even sooner than expected. Given that we are a relatively large and creative group of individuals and the energetic nature of the environment in which we work, I truly believe that we have what it takes to accomplish in answering this question.

As I have developed a method to my practice (and madness) as an emergency medicine pharmacist, there are certain medications that, for me, fall under one of two categories: those that I have grown to love…and those that I have grown to not be a fan of and can generally live without, even in the absence of drug shortages.

For me, parenteral hydralazine falls under the latter category.

Why?

As many of us already know, hydralazine is a potent vasodilator that has direct actions on the vascular smooth muscle, leading to arterial vasodilation primarily. It is thought to work through inhibition of the release of calcium into smooth muscle cells within the vasculature through a number of mechanisms, which include induction of cyclic guanosine monophosphate (cGMP), generation of nitric oxide, and hyperpolarization of cell membranes.

The issues that many encounter related to the effects of hydralazine are mainly due to its pharmacokinetic properties. It has an onset of action of upwards of 20 minutes, with peak effects last for 60 minutes. However, duration of action is somewhat prolonged and unpredictable compared to other parenteral agents available for hypertensive crises; the effects of hydralazine can persist for upwards of eight hours. A review article published (ironically) in the Journal of Emergency Medicine nearly two decades ago highlights some of the factors associated with these effects (1), which includes the fact that the active metabolites of hydralazine may tend to stick around for some time. Another possible reason is that the drug may actually bind to the tissue within the arterial wall itself, which has been demonstrated in a number of animal studies. A third plausible explanation is the idea that hydralazine may have a continuous effect on endothelium-derived relaxing factor, which is a molecule that signals the cells within the smooth muscle to dilate.

In addition, the adverse effects of hydralazine are not benign either. Hydralazine is generally not recommended in patients with cardiovascular comorbidities such coronary artery disease, aortic dissection, and valvular dysfunction, as it can cause stimulation of the sympathetic nervous system, leading to exacerbation of oxygen consumption in a myocardium (which may be already compromised to begin with) as well as an increase in heart rate. In addition, in patients with disrupted cerebral autoregulation, hydralazine has been demonstrated to be associated with increasing intracranial pressure (2-4).

Some may argue that hydralazine does have a specific role within the emergency department, especially when it comes to managing patients who may present with pregnancy-associated hypertension. However, hydralazine is not gentle in its adverse effect profile, as patients may experience severe hypotension and complications associated with birth. If labetalol fails or is not an option, reasonable alternative agents that may be used in this setting include nicardipine and sodium nitroprusside (5-8).

And for those who still wish to use parenteral hydralazine for admitted patients, great vigilance should be taken to ensure that the use of this agent is appropriate. One retrospective study analyzed prescribed orders of parenteral hydralazine in 94 patients over a six-month period to evaluate clinical parameters prior to and following administration of hydralazine, including evidence of target-organ damage and/or symptoms associated with severe hypertension, change in blood pressure and heart rate, and the incidence of adverse effects (9). The investigators found that only 2% of all patients who were prescribed hydralazine had documented evidence of hypertensive crisis. Over 80% of all doses of hydralazine that were administered within this time frame were associated with a reduction in systolic blood pressure of less than 25%. Of the 16 patients who experienced an adverse effect, most were related to hypotension, with six of those patients experiencing a decrease in systolic blood pressure by at least 65 mmHg. In addition, investigators of a recently published multicenter study found that hydralazine was commonly implicated with profound hypotension in the critical care setting (10).

As with anything, increasing provider awareness and education is essential, and verifying that the right circumstances are in place with thorough patient evaluation prior to administration of parenteral hydralazine, including confirmation of the fact that all possible alternatives for managing blood pressure have been optimized prior to initiation of this agent, is critical.

For now, parenteral hydralazine is in fact on a nationwide shortage and the resupply date through various manufacturers is still unknown (11). However, I am certainly not missing it in my practice in the emergency department anyway. References:

1. Powers DR, Papadakos PJ, Wallin JD. Parenteral hydralazine revisited. J Emerg Med 1998; 16:191-196.
2. Ludden TM, Shepherd AM, McNay JL, et al. Hydralazine kinetics in hypertensive patients after intravenous administration. Clin Pharmacol Ther 1980, 28:736-742.
3. Rhoney DH, Liu-DeRyke X. Effect of vasoactive therapy on cerebral circulation. Crit Care Clin 2006; 22:221-243.
4. Skinhoj E, Overgaard J. Effect of dihydralazine on intracranial pressure in patients with severe brain damage. Acta Med Scand Suppl 1983; 678:83-87.
5. Emergent therapy for acute-onset, severe hypertension with preeclampsia or eclampsia. Committee Opinion No. 514. American College of Obstetricians and Gynecologists. Obstet Gynecol 2011; 118:1465-1468.
6. Arulkumaran N, Lightstone L. Severe pre-eclampsia and hypertensive crises. Best Pract Res Clin Obstet Gynaecol 2013; 27:877-884.
7. Magee LA, Cham C, Waterman EJ, et al. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ 2003; 327:955-960.
8. Alexander JM, Wilson KL. Hypertensive emergencies of pregnancy. Obstet Gynecol Clin North Am 2013; 40:89-101.
9. Campbell P, Baker WL, Bendel SD, et al. Intravenous hydralazine for blood pressure management in the hospitalized patient: its use is often unjustified. J Am Soc Hypertens 2011; 5:473-477.
10. Kane-Gill SL, Leblanc JM, Dasta JF, et al. A multicenter study of the point prevalence of drug-induced hypotension in the ICU. Crit Care Med 2014; 42:2197-2203.
11. Drug Shortages: Hydralazine Injection. American Society of Health-System Pharmacists. Available at: http://bit.ly/1oTPepf [Accessed 8 October 2014]