Thursday, May 22, 2014

EMPOWER Podcast Episode 1 - The Next Step In Upstairs Care, Downstairs

The link to the podcast in iTunes is here.

Episode 1: The Next Step in Upstairs Care, Downstairs

Show Notes:

The research and evidence for emergency medicine pharmacists is out there in mass quantity. The ASHP Emergency Care section has done the most complete collection of the existing data and links to the manuscripts.

Selected citations:
  • Medication errors occur in up to 60% of ED patients - Patanwala AE, Warholak TL, Sanders AB, et al. A prospective observational study of medication errors in a tertiary care emergency department. Ann Emerg Med. 2010;55:522-526
  • EM pharmacists’ care reduces medication errors – PI is an MD - Rothschild JM, Churchill W, Erickson A, et al. Medication errors recovered by emergency department pharmacists. Ann Emerg Med. 2010;55:513-521.
  • “The pharmacists’ nominally assigned activity—reviewing medication orders—was less important in preventing medication errors than their general availability for discussion and consultation.” – Patanwala AE, Sanders AB, Thomas MC, et al. A prospective, multicenter study of pharmacist activities resulting in medication error interception in the emergency department. Ann Emerg Med. 2012;59:369-373 was a great site run by one of the icons of EM pharmacy – Dan Hays. Unfortunately I do not think it is updated anymore. However, all the resources are still there, and worthwhile checking out.

While this data is plentiful, I do have to admit, from a purely skeptical view of things, each paper is written largely (if not exclusively) by pharmacists.  Clearly, we have a vested interest in finding positive results, and there may be some publication bias with respect for other trials where no benefit of an EMP was found (I can already hear the “they took our jobs” in Southpark dialect). But with that said, there is ample opportunity for fair and balanced investigation.

The Institute for Safe Medication Practices (ISMP)  -
Defining a medication error: “A medication error is “any error occurring in the medication use process”
Defining the medication use process: “Medication use is a complex process that comprises the sub-processes of medication prescribing, order processing, dispensing, administration, and effects monitoring.”

Here is the an excerpt from the ACEP website discussing the Joint Commission mandate: (

The Joint Commission has once again changed its standard requiring first dose, prospective pharmacy review -- a move that should provide some relief to emergency departments nationwide.
The revised standard now allows for an exception to the rule "in urgent situations," and frees the emergency physician from actually being required to order, prepare and administer the medication by allowing a registered nurse to process and administer the medication if a physician is in the proximity of the patient.
The revisions came after several months of ACEP representatives working with the Joint Commission to find a solution to the concerns facing emergency departments with the standard. ACEP joined forces with AAEM and ENA, and wrote several letters to the Joint Commission since the standard begin Jan. 1. A Joint Commission task force that includes ACEP members will continue to monitor the standard.

"We are pleased that the Joint Commission heard the concerns of the emergency physicians," said Marilyn Bromley, RN, ACEP’s Director of EM Practice. "We believe these changes still keep the standard’s intent of providing patient safety, but allow for a process in the ED that still manages patient throughput and minimizes treatment delays."

Perhaps it's time to address this argument once again, but with a different approach to what and how pharmacists can contribute to emergency medicine.

Monday, May 19, 2014

The (Phosphate) Salt and Pepper of Common EM Medications

Drug delivery has always been a fascinating subject for me. Some of us may take for granted the countless hours dedicated toward the research, design, and development of new drugs and delivery systems in order to optimize the ability for a drug is able to reach its site of action; essentially, to make sure that the drug that we think will work will actually "do its thing."

One such mechanism of enhancing drug delivery is through the design of prodrugs, which are derivatives of drug molecules that undergo an enzymatic process within the body to release the active drug, which will in turn, exhibit its desired effect. This is usually done to overcome barriers related to the physiochemical and/or pharmacokinetic properties of the active moiety, and in most instances, the solubility and permeability of the drug in various tissues and substances is enhanced with the prodrug. 

Phosphate esters are one example of prodrugs that are designed to increase the aqueous solubility of a number of compounds, especially those with side chains containing amino and/or hydroxyl groups. By taking advantage of the presence of endogenous enzymes such as alkaline phosphatase, the prodrug can undergo biotransformation to its active moiety. One drug that is commonly used in the emergency department (ED) that is considered to be a phosphate ester prodrug is fosphenytoin, which is approximately 7000 times more soluble than phenytoin, lending it to have a number of advantages such as rapid conversion within the bloodstream to phenytoin and reduced local irritation due to decreased precipitation at the site of injection. Another classic example of a phosphate salt that is commonly prescribed in the ED is dexamethasone sodium phosphate (commonly known as Decadron). 

At this point, you may be thinking, "Great. So who cares about a phosphate group?"

While phosphate esters pose these great advantages, they do have one pitfall specifically associated with their route and rate of administration that some clinicians may not necessarily be cognizant of when it comes to prescribing these medications. This is especially true as order sentences within our computerized provider order entry (CPOE) systems may be sophisticated enough to take into account the untoward adverse effect associated with these salts and may prevent prescribers from ordering these medications a certain way.

What is this adverse effect that I am alluding to? Believe it or not, it is perineal pruritus.

While several case reports and controlled studies have been published regarding this adverse effect, unfortunately, the mechanism is not clearly understood. However, it is thought to be due to the phosphate group on these compounds, and commonly occurs as the drug is given as a rapid intravenous (IV) push. This same adverse effect was also demonstrated with rapid IV infusion of the agent fospropofol (which, as a side note, interestingly enough, has been discontinued from the US market since June 2012). The effect and any pain associated with perineal pruritus subsides as hydrolysis of the prodrug to the parent compound occurs, and there are generally no long-term consequences of the effect for the patient (other than the lasting memory of experiencing such an unpleasant reaction).

The potential of this adverse effect associated with these phosphate salts can be minimized in one of two ways. Both fosphenytoin and dexamethasone sodium phosphate can be administered as an intramuscular injection as an alternative route of administration. If IV access is obtained and necessary, dexamethasone can be mixed in 50 mL of diluent and given as an IV piggyback over five to ten minutes. In the case of fosphenytoin, we know that the rate of administration should not exceed 150 mg/min, and so this rate should be taken into account when administering the drug to a patient via the IV route.

Although much effort is exercised to ensure adequate delivery of a drug through the body, regardless of how well-intentioned efforts may be, the potential consequences can certainly be unanticipated and may go unrecognized as being associated with the drug delivery system of the compound. As the saying goes, "With great power...comes great responsibility."

Selected References:

Huttunen KM, Raunio H, Rautio J. Prodrugs: from serendipity to rational design. Pharmacol Rev 2011; 63:750-771.

Perron G, Dolbec P, Germain J, et al. Perineal pruritus after IV dexamethasone administration. Can J Anaesth 2003; 50:749-750.

Singh M, Sharma CS, Rautela RS, et al. Intravenous dexamethasone causes perineal pain and pruritis. J Anesthe Clin Res 2011; S1:001.

Eldon MA, Loewan GR, Voightman RE, et al. Pharmacokinetics and tolerance of fosphenytoin and phenytoin administration intravenously to healthy subjects. Can J Neuro Sci 1993; 20:S810.

Pruitt RE, Cohen LB, Gibiansky E, et al. A randomized, open-label, multicenter, dose-ranging study of sedation with Aquavan injection (GPI 15715) during colonoscopy. Gastrointest Endosc 2005; 61:AB111.

Wednesday, May 7, 2014

Epinephrine Autoinjectors: An Automatic Replacement?

Part of my responsibility as a pharmacist for the ED includes reviewing medication-related incident reports. I recently came across one case in which a nurse administered 0.3 mg of 1:1000 epinephrine for an anaphylactic reaction by the intravenous (IV) route instead of the intended intramuscular (IM) route. The nurse that gave the medication immediately recognized the error, called the ED attending physician to the bedside, and the patient was closely monitored until the effects of the epinephrine dissipated. It is well documented that when administered to a patient with a pulse, inadvertent IV administration of 1:1000 epinephrine can cause life-threatening hypertension, dysrhythmias, and myocardial ischemia.1

Published case reports demonstrate that accidental administration of 1:1000 epinephrine via the IV route can lead to unplanned ICU admission, intubation, and acute kidney injury requiring renal transplant.2-7 Fortunately, the patient was young, otherwise healthy, and experienced no residual effects.

Our process for epinephrine administration in this scenario included withdrawing an epinephrine 1:1000 ampule (1 mL) from an automated dispensing cabinet. The ampule is packaged in a small bag with a warning sticker placed on the outside of the bag that states “For IM or SUBQ use only, not for IV use.” When patients present with anaphylaxis, a verbal order from the ED physician to the nurse occurs for epinephrine. Other medication safety measures in place elsewhere throughout our institution (e.g. bedside medication barcode scanning) are not currently used in the ED. This results in a potential for medication errors to occur and indeed, this is not unique to our ED. In a retrospective analysis of ED patients presenting with anaphylaxis over a five year period, one ED documented a 2.4% incidence of potentially life-threatening complications from inappropriate epinephrine administration.8

Very few drugs have their concentrations expressed as ratio strength (e.g. 1:1000 or 1:10, 000) instead of mass concentration (e.g. micrograms per milliliter). This method of expressing concentration represents the amount of solution (in milliliters) used to dilute 1000 mg of epinephrine. For example, the 1:10,000 solution uses 10,000 milliliters of solution to dilute 1000 mg of epinephrine, resulting in a 0.1 mg/mL concentration. In a randomized classroom simulation study of physicians, epinephrine labeled with ratio strength instead of mass concentration was more likely to be administered incorrectly (OR 13.4, 95% CI 2.2 – 81.7).9 This, in combination with the potentially devastating consequences if administered incorrectly, makes the topic of errors related to epinephrine in the ED ripe for discussion.

As is sometimes the case after an error like this occurs, ED staff looked to the pharmacy to help formulate a safer solution. One of the ED physicians suggested using only the EpiPen™ autoinjectors for this indication. This would prevent the previously described incident for both adult and pediatric patients (with the only exception being pediatric patients weighing less than 15 kg, for whom the 1:1000 ampule would still be used). After discussion with the involved parties, the “solution” was implemented.

It wasn't long until I started to receive complaints from staff regarding the practice change. Currently, pre-hospital personnel in our area are equipped with the 1:1000 epinephrine ampules for anaphylactic reactions; why couldn't nurses be trusted to administer the drug appropriately? Several nurses expressed apprehension over having to use the bigger, more painful needle of the autoinjector. Some ED physicians sympathized with this concern and started ordering non-standard doses of epinephrine for this indication just so that they could use the ampule instead of the autoinjector. There have even been documented reports (including some anecdotal reports from my own ED) of providers attempting to use the EpiPen and inadvertently injecting the medication into their own thumb instead.10-14 Surprisingly, one of the biggest concerns voiced from the ED staff was regarding the cost difference between the two products. As a pharmacist, I’m used to being one of the only parties interested in drug cost. In this situation, I most certainly was (with a nearly 150-fold difference in our acquisition costs between the two products), but tried to weigh this against the potential benefit of patient safety.

This issue came up just recently on an e-mail listserv of ED pharmacists. Of seven respondents, four were against use of the autoinjector (they preferred the ampules), and three were in support of the autoinjector. Pharmacists described struggling with the same issue at their respective institutions, and the shortcomings of both options were acknowledged. No one seemed to have figured out an ideal solution.

After experimenting with the autoinjector option for several months and listening to the concerns of the ED staff, another solution was proposed. We currently have a process in place for several medications designated as “high alert” which requires a dual nursing sign off in the electronic medical record (EMR) to verify appropriateness (e.g. insulin and heparin administration). Even if the nurse administers the medication prior to charting the administration in the EMR, it has become part of the routine nursing workflows to have another nurse verify the right patient, right time, right drug, right dose, and right route (commonly referred to as “the 5 rights”). We decided to make epinephrine administration for this indication a dual sign off in the EMR with the hopes that having a second nurse double-check could decrease the risk of a medication error. Additionally, we would transition back to using the 1:1000 ampules and reserve the EpiPen autoinjectors for outpatient use.

The same authors that described the incidence of epinephrine dosing errors in anaphylaxis at their institution proposed several measures to decrease errors.8 They suggested using warning stickers placed on epinephrine, performing educational outreach to staff, increasing pharmacist availability, and interestingly, using only autoinjectors on all of the crash carts and in patient care areas where an anaphylactic reaction could occur. From my experience at our institution, I would not be an advocate for stocking EpiPen autoinjectors on all crash carts. Not only for the extraordinarily high cost/low frequency of use ratio, but also because that “solution” comes with its own set of problems. Perhaps our dual sign-off workflow can help to encourage perhaps the most effective safeguard in this situation: the 5 rights.

Meghan E. Groth, Pharm.D., BCPS
Emergency Medicine Pharmacy Clinician, Fletcher Allen Health Care

Edited by: Nadia Awad, Pharm.D., BCPS (@Nadia_EMPharmD)        

1. Soar J, Pumphrey R, Cant A, et al. Emergency treatment of anaphylactic reactions-guidelines for healthcare providers. Resuscitation 2008; 77:157-169.
2. Dybvik T, Halvorsen P, Steen PA. Accidental intravenous administration of 50 mg of racemic adrenaline in a 2-year-old boy. Eur J Anesthesiol 1995; 12:181-183.
3. Karch S. Coronary artery spasm induced by intravenous epinephrine overdose. Am J Emerg Med 1989; 7:485-488.
4. Novey HS, Meleyco LN. Alarming reaction after intravenous administration of 30 mL epinephrine. JAMA 1969; 207:243-246.
5. Horek A, Raine R, Opie LH, et al. Severe myocardial ischemia induced by intravenous adrenaline. BMJ 1983; 268:519.
6. Hall AH, Kulig KW, Rumack BH. Intravenous epinephrine abuse. Am J Emerg Med 1987; 5:64-65.
7. Ferry DR, Henry RL, Kern MJ. Epinephrine-induced myocardial infarction in a patient with angiographically normal coronary arterias. Am Heart J 1986; 111:193-195.
8. Kanwar M, Irvin CB, Frank JJ, et al. Confusion about epinephrine dosing leading to iatrogenic overdose: a life-threatening problem with a potential solution. Ann Emerg Med 2010; 55:341-344.
9. Wheeler DW, Carter JJ, Murray LJ, et al. The effect of drug concentration expression on epinephrine dosing errors: a randomized trial. Ann Intern Med 2008; 148:11-14.
10. Mathez C, Favrat B, Staeger P. Management options for accidental injection of epinephrine from an autoinjector: a case report. J Med Case Rep 2009; 3:7268-7270.
11. Sellens C, Morrison L. Accidental injection of epinephrine by a child: a unique approach to treatment. CJEM 1999; 1:34-36.
12. Simons F, Lieberman P, Read E, et al. Hazards of unintentional injection of epinephrine from autoinjectors: a systematic review. Ann Allergy Asthma Immunol 2009; 102:282-287.
13. McGovern S. Treatment of accidental digital injection of adrenaline from an auto-injector device. J Accid Emerg Med 1997; 14:379-380.
14. Fitzcharles-Bowe C, Denkler K, Lalonde D. Finger injection with high-dose (1:1000) epinephrine: dose it cause finger necrosis and should it be treated? Hand 2007; 2:5-11.

Monday, May 5, 2014

100: Introduction to EMPOWER

Pharmacists exist in somewhat of a gray area in terms of the care of emergency department patients. In no other environment are pharmacists generally absent in the medication use process as in emergency departments. Yet, the very nature of the atmosphere of emergency medicine can produce significant and unnoticed medication errors. As pharmacists practicing in the emergency department, we tend to have a different point of view from other clinicians on the team. While the exact definition of what an emergency medicine pharmacist is unclear, it is something we have been striving to define. Our training and druggist minds lead us to focus on medications and be analytical with regards to the reasoning and methods behind why we do the things we do. Because we can afford to do so, we can even challenge some of the myths and misconceptions related to the use of medications in general, and specifically those commonly utilized in the emergency department.

It has been a little over a year and a half since we first started this blog. We sought to fill in a gap within the great emergency medicine blogs in existence when we started this project of sorts back in September 2012. Sure, some blogs did (and still do) cover some aspects related to pharmacy in emergency medicine, but generally not from the perspectives of pharmacists. And so, with this, in sharing our experiences and describing patient scenarios that we come across in our day-to-day practice, we hoped to really be able to offer our readers an understanding of our role in the emergency department, and allow for an exchange of ideas between our readers and us writers.

As writing goes, you always hear that in order to become a better writer, write more. Starting this blog, we hoped to be able to improve our own writing, and thought the process grew as critical (even skeptical) reviewers of the latest and greatest in emergency medicine. Ultimately, it has, and continued to, help strengthen our own clinical practice, which is something that we hold very valuable and wish to continue to maintain over the course of our practice.

Believe it or not, this is our 100th post. For something that began as an experiment all the way up until this point, it has been an amazing ride. Making connections with our readers virtually first via Twitter and through #FOAMed that are followed up with live meetings in person has been probably one of our best experiences yet. It has been awesome realizing that we are not the only ones who believe that this endeavor is worthy of scholarly merit. Granted, we are not doing this for that purpose at all, and we believe it would really put a dent for either one of us pursuing this any further if we were told by our department chairs that we needed to write on this blog once every two weeks. At the same time, it is hard to deny the the fact that others within the #FOAMed community have really come a long way in utilizing this form of social media to advance their professional and career development. To us, that is just an added virtue to this endeavor, but again, that was not our intent in the first place. Hopepfully, our efforts will transform the #FOAMed movement in pharmacy from the immovable object to the unstoppable force.

With all of this, we began to think about where we wanted to go next with the blog. How can we really put a voice out there for emergency medicine pharmacists? How can we allow others to gain a better understanding and appreciation for the role of pharmacists in the emergency department?

And so we provide you with a sneak peek at our next undertaking in the world of #FOAMed. Ladies and gentlemen, we would like to introduce to you our newest project: EMPOWER.

Please be sure to spread the word. We hope to continue to expand on the theme of this blog in covering topics related to the practice of pharmacy within emergency medicine, and we plan on bringing on special guests and fellow EM pharmacists to help make this podcast all the better. Our goal is to really help enhance the voice of pharmacy within emergency medicine.

To those of you who directly encouraged us to pursue this podcast as our next project, thank you for giving us that extra push. We sure did need it.

As always, we welcome questions, comments, and suggestions related to our blog and podcast. Please feel free to send us a message or a comment, or even tweet a question to either one of us. Thank you for loyally following this blog, and for all of your support.

Nadia Awad, Pharm.D., BCPS, and Craig Cocchio, Pharm.D., BCPS
The Blog Team of Emergency Medicine PharmD

Featured Post

Giapreza - A Closer Look at the Pharmacology of Ang2

Angiotensin-II (Ang2) is now an FDA approved vasopressor. With this new addition to the available options, experts are combing over the ...